Abstracts 1 / 18 / 16 A . Development of the Nervous System Class - 6 Semaphorins have receptor function during neural circuit

s 1/18/16 A. Development of the Nervous System Class-6 Semaphorins have receptor function during neural circuit formation A6 Authors Vlad Karas (1), Irwin Andermatt (1), Olivier Mauti (1), Esther Stoeckli (1) Affiliations 1) University of Zurich Class-6 Semaphorins form a transmembrane subgroup of the Semaphorin family. They were implicated in various processes, such as differentiation, cell migration, and angiogenesis. However, in most of these processes they were shown to act as ligands of Plexin receptors. Evidence for a receptor functions was suggested based on our studies on Sema6A’s role in the formation of boundary cap cell clusters, a gate keeper structure between the peripheral and the central nervous system during development (Mauti et al., Neural Development, 2(2007)28). Loss of Sema6A in boundary cap cell precursors resulted in motoneurons exiting the spinal cord along the ventral roots, and in the failure of dorsal roots to form properly. Loss of Sema6D had an effect only at the dorsal root entry site but did not result in the loss of motoneurons from the spinal cord. More recently, we demonstrated a cell-autonomous role of Sema6B as a receptor in commissural axon guidance (Andermatt et al., Development 141(2014)3709-3720). In the absence of Sema6B, post-crossing commissural axons failed to turn rostrally along the longitudinal axis of the spinal cord. A cisversus trans-interaction between Sema6B and its binding partner PlexinA2 was shown to regulate responsiveness of commissural axons at the midline. We have now extended our analysis of class-6 Semphorins’ function during neural development to the peripheral nervous system. We used the chicken embryo to individually downregulate each member of the family (Sema6A, Sema6B and Sema6D) and study aberrations in axon guidance using whole-mount staining. Disruption of Sema6 signaling resulted in abnormalities in the crural, sciatic and epaxial nerves at E5 (HH25). Together, these findings suggest an important, previously unexplored role for class 6 Semaphorins in PNS neural circuit formation. A Wnt signaling network is required for axon guidance A7 Authors Evelyn Aviles (1), Esther Stoeckli (1) Affiliations 1) University of Zurich, Winterthurerstrasse 190, 8057 Zurich For the formation of neural circuits, axons have to be guided to their appropriate target cells by a combination of attractive and repulsive cues. Recently, we have shown that Wnt5a and Wnt7a act as attractants for post-crossing commissural axons in the spinal cord of chicken embryos. However, the molecular signaling pathways activated by Wnts during axon guidance are not completely understood. In addition to atypical protein kinase C, members of the Wnt planar cell polarity (PCP) pathway were implicated in commissural axon guidance in the mouse. We confirmed that PCP components are also required for post-crossing commissural axon guidance in the chicken spinal cord. However, taking advantage of the precise temporal control of gene silencing provided by in ovo RNAi, we demonstrate that canonical Wnt signaling is also required for proper guidance of postcrossing commissural axons in the spinal cord. Furthermore, rescue experiments showed that canonical Wnt activity is required cell autonomously. Taken together, these studies show that Wnt signaling in axon guidance SSN Annual Meeting 1/18/16 1 / 67 cannot be reduced to one of the well-known signaling pathways. Rather, Wnt activates a complex network of intracellular signaling components. The pharmacological blockade of Na+/Ca2+ exchanger modulates the growth and development of Purkinje cell dendritic arbor in mouse cerebellar slice cultures. A8 Authors Pradeep Sherkhane (1, 2), Josef P. Kapfhammer (1, 2) Affiliations 1) Anatomical Institute, Department of Biomedicine 2) University of Basel Purkinje cells are the most distinctive neurons in the cerebellar cortex because of their unique and intricate dendritic arbor. We have earlier shown that chronic activation of type I metabotropic glutamate receptors severely inhibits Purkinje cell dendritic growth. The stunted dendritic growth seen after mGluR1 activation is rescued by the blockade of PQ-type and T-type Ca2+ channels. Similarly, Plasma membrane calcium ATPase 2 (PMCA2) blockade also moderately inhibits the growth of the Purkinje cell dendritic arbor. But, in combination with mGluR1 activation rescues the dendritic reduction of Purkinje cells. These findings suggest that influx and efflux of calcium plays an instrumental role in the development of the Purkinje cell dendritic arbor. The sodium-calcium-exchanger (NCX) is a plasma membrane calcium exchange mechanism with bidirectional modes: the forward mode (Ca2+ efflux mode) and reverse mode (Ca2+ influx mode). We inhibited these modes by pharmacological compounds to study their effects on the development of Purkinje cell dendritic arbor. The blockade of forward mode by Bepridil moderately inhibited growth of the Purkinje cell dendritic arbor and blockade of the reverse mode by KB-R7943 strongly reduced the size of the dendritic arbor and induced thickened distal dendrites. The use of Bepridil and KB-R7493 together had a profound negative impact on the dendritic development in Purkinje cells. To investigate the role of sodium-calcium-exchanger in depth, we added benzyloxyphenyl derivatives like YM-244769 and SN-6 in the study which preferentially block the reverse mode like KB-R7943. In parallel, the derivatives like CB-DMB and ORM10103 were also tested which have specificity for both outward and inward currents of Na+/Ca2+ exchanger. These compounds showed similar effects on dendritic arbor development except the thickened distal dendrites seen in KB-R7943 treated slice cultures, suggesting that this phenotype might be unrelated to blockade of the reverse mode. We speculate that thickened distal dendritic phenotype might be due to non-specific actions of KB-R7943 against ion channels, neuronal nicotinic acetylcholine receptors, the N-methyl-D-aspartate receptor or norepinephrine transporter. Our findings show that interfering with the function of the Na+/Ca2+ exchanger profoundly affects Purkinje cell dendritic growth probably by altering the calcium equilibrium within Purkinje cell dendrites. The role of DiGeorge Critical Region 2 gene in cortical circuit formation A9 Authors Aude Chenu (1), Alexandre Dayer (1) Affiliations 1) Department of mental health and basic neuroscience, University of Geneva Using in vivo cell-type specific manipulation of pyramidal neurons progenitors, we aim to investigate the role of DiGeorge Critical Region 2 (DGCR2) on cortical circuit formation, a critical process involved in schizophrenia vulnerability. DGCR2 is located in the 22q11.2 locus, whose deletion is one of the highest known risk factor for schizophrenia (SZ), and codes for a transmembrane protein expressed during cortical development. SSN Annual Meeting 1/18/16 2 / 67 Interestingly, exome sequencing revealed a de novo DGCR2 mutation in an idiopathic schizophrenic patient. Here we aimed to investigate the role of DGCR2 in early steps of cortical circuit formation using in utero electroporation targeted to pyramidal neurons (PNs). Knock-down of the expression of mouse (m)DGCR2 during corticogenesis affected the laminar positioning of PNs in a persistent manner in the somatosensory cortex and the medial prefrontal cortex. DGCR2-shRNA-induced mispositioning could be fully rescued by overexpressing the human (h)DGCR2, which is not targeted by the mDGCR2-shRNA. In contrast, (h)DGCR2 containing the de novo mutation was not able to fully rescue the DGCR2-shRNA-induced mispositioning phenotype, indicating a functional role for this mutation. In order to further understand the biological function of DGCR2, we are currently investigating the role of specific DGCR2 subdomains and studying potential binding partners. These studies will allow us to understand the role of the SZ-risk gene DGCR2 on cortical circuit assembly. Effect of neuronal erythropoietin on postnatal neurodevelopment A12 Authors Kasifa Khalid (1), Christina Köster-Hegmann (1), Prof. Dr. Jean-Marc Fritschy (1), Prof. Dr. Max Gassmann (2), Dr. Edith M. Schneider Gasser (1, 2) Affiliations 1) Institute of Pharmacology & Toxicology, UZH 2) Institute of Veterinary Physiology, UZH Erythropoietin (Epo) is a hypoxia inducible hormone mainly known for its role in erythropoiesis. Epo is also found in the brain, where its expression is highest during embryonic development and then rapidly reduces perinatally. Epo’s brain expression during development suggests an important physiological role for this hormone. Our work evaluated Epo’s function in postnatal neurodevelopment. For this purpose, we used a mouse model which constitutively overexpresses Epo in the brain (Tg21). In these mice normal haematological parameters were preserved but brain volumes at perinatal ages were enhanced. Neurogenesis, proliferation and maturation of neurons was evaluated at different postnatal developmental stages. We show a faster postnatal neurodevelopment in the Tg21 mice, affecting mainly the inhibitory GABAergic system. With this work, we have described a novel physiological function for cerebral Epo in vivo, showing its role in differentiating neuronal precursor cells. Interaction between Redox dysregulation and Neuroinflammation during early development could lead to PVI circuitry impairments in adulthood: relevance for schizophrenia A13 Authors Daniella Dwir (1), Jan-Harry Cabungcal (1), Liliane Tenebaum (2), Pascal Steullet (1), Michel Cuénod (1), Rabindra Tirouvanziam (3), Kim Q. Do (1) Affiliations 1) Center for Psychiatric Neuroscience, DP, CHUV, Lausanne, Switzerland 2) Cellular and Molecular Neurotherapy, Department of Clinical Neuroscience, CHUV, Lausanne, Switzerland 3) Research Emory University School of Medicine, PACS, Atlanta, GA, USA Schizophrenia (SZ) is a major psychiatric disease which involves both genetic and environmental factors. Glutathione (GSH), a main cellular antioxidant and redox regulator, is decreased in CSF and brain of patients. The key GSH synthesizing genes present polymorphisms associated with the disease. Thus, a redox dysregulation during neurodevelopment may be a critical risk factor for SZ when genetic vulnerability for redox SSN Annual Meeting 1/18/16 3 / 67 dysregulation and environmental stressors generating oxidative stress converge. Moreover, oxidative stress is known to induce inflammation. Anomalies in peripheral immune cells as well as dysregulation of immune-related genes have been reported in SZ. The interaction between both processes occurring at critical period during brain development may affect neurons vulnerable to elevated oxidative insults, such as parvalbumin-expressing interneurons (PVI), which circuit is impaired in postmortem SZ brain. Mature cortical PVI are usually surrounded by a perineuronal net (PNN), which might be degraded by matrix metalloproteinases (MMPs), induced in pro-inflammatory condition and activated by oxidative stress. We used a transgenic mouse model with GSH deficit (GCLM -/-) that shows SZ related phenotype, to investigate the interaction between oxidative stress and neuroinflammation in early development, to account for the aversive effect on PVI/PNN circuitry in adult.We compared PVI, PNN and microglia level in the anterior cingulate cortex (ACC) of GCLM-/and WT mice at peripuberty and in adulthood. In addition, mice were treated with a dopamine reuptake inhibitor (GBR) to pharmacologically induce additional oxidative insult from postnatal days (P) 10 to 20. GBR treatment in young mice led to a decreased PVI+ and PV-PNN+-IR, increased oxidative stress level and microglia activation in adult GCLM-/-, showing the tight interaction between the redox and inflammatory state. Microglia activation was more pronounced at peripubertal stage compared to adulthood, suggesting a stage specific vulnerability in GCLM-/-. We explored the role of RAGE, which is activated by ligands produced by oxidative stress, and found increased RAGE shedding in neurons as well as increased MMP9-IR in GCLM-/at P40. Interestingly, a specific inhibitor of MMP9 prevented RAGE shedding and microglia activation in the ACC of P40 GCLM-/-, demonstrating the involvement of MMP9 and suggesting that this treatment could also limit oxidative stress and PVI/PNN deficit. We propose that an interaction between redox dysregulation and pro-inflammatory condition via RAGE/MMP9 in early development is a potential trigger of structural and morphological impairments in adult. B. Molecular and Cellular Mechanisms: Dell-Cell Interaction Heterogeneity of Radial Glia-Like Cells in the Adult Hippocampus B1 Authors Elias Gebara (1), Michael Bonaguidi (2), Ruth Beckervordersandforth (3), Sébastien Sultan (1), Florian Udry (1), Pieter-Jan Gijs (1), Dieter Chichung Lie (3), Guo-li Ming (4), Hongjun Song (4), Nicolas Toni (1) Affiliations 1) Department of Fundamental Neuroscience, University of Lausanne, rue du Bugnon, Lausanne, Switzerland 2) Eli and Broad CIRM Center for regenerative Medicine and Stem Cell Research, University of Southern California, 1425 San Pablo Street, Los Angeles, CA 90033, USA 3) Institute of Biochemistry, Friedrich-Alexander Universität, Erlangen-Nürnberg, Fahrstrasse 17, 91054 Erlangen, Germany 4) The Solomon Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA Adult neurogenesis is tightly regulated by the neurogenic niche. Cellular contacts between niche cells and neural stem cells are hypothesized to regulate stem cell proliferation or lineage choice. However, the structure of adult neural stem cells and the contact they form with niche cells are poorly described. Here, we characterized the morphology of radial glia-like (RGL) cells, their molecular identity, proliferative activity, and fate determination in the adult mouse hippocampus. We found the coexistence of two morphotypes of cells with prototypical morphological characteristics of RGL stem cells: Type a cells, which represented 76% of all RGL cells, displayed a long primary process modestly branching into the molecular layer and type b cells, which represented 24% of all RGL cells, with a shorter radial process highly branching into the outer granule SSN Annual Meeting 1/18/16 4 / 67 cell layer-inner molecular layer border. Stem cell markers were expressed in type a cells and coexpressed with astrocytic markers in type b cells. Consistently, in vivo lineage tracing indicated that type a cells can give rise to neurons, astrocytes, and type b cells, whereas type b cells do not proliferate. Our results reveal that the adult subgranular zone of the dentate gyrus harbors two functionally different RGL cells, which can be distinguished by simple morphological criteria, supporting a morphofunctional role of their thin cellular processes. Type b cells may represent an intermediate state in the transformation of type a, RGL stem cells, into astrocytes. Control of adult and aging hippocampal neurogenesis by astrocytic released molecules B2 Authors Frédéric Cassé (1), Sebasiten Sultan (1), Elias Gebara (1), Nicolas Toni (1) Affiliations 1) Department of Fundamental Neurosciences, University of Lausanne, Switzerland Throughout life, adult neurogenesis occurs in the hippocampus and provides new neurons continuously to the dentate gyrus. The cellular environment of adult neural stem cell (aNSCs), named the neurogenic niche, regulates their proliferation and is composed of various cell types. One major cell type of the neurogenic niche is astroglia. In this study, we investigated the effect of astrocytic released molecules on the mouse hippocampal adult neurogenesis in the adult and aging brain. Interestingly, we found that astrocyte-conditioned medium increased aNSC proliferation in vitro and in vivo in the dentate gyrus of adult and old mice. The active molecules involved in this effect on aNSC proliferation have a molecular weight inferior to 3 kilodalton and target the NMDA receptor. Moreover, blocking the astrocytic vesicular release reduced aNSC proliferation both in vitro and in vivo. These results indicate that astrocytes release molecules that could regulate hippocampal neurogenesis in adult and aging brain. Modulating astrocytic exocytosis in the hippocampus could be an interesting therapeutic strategy in order to control neurogenesis in pathological conditions. VMAT2 in astrocytes regulates morphology of pyramidal neurons in developing PFC by modulating extracellular levels of dopamine B3 Authors Luca Pucci (1), Tamara Zehnder (1), Francesco Petrelli (1), Corrado Calì (1), Frank Kirchhoff (3), Nicole Déglon (4, 5), Bruno Giros (6, 7), Robert H Edwards (8), Jean-Pierre Mothet (2), Paola Bezzi (1) Affiliations 1) Department of Fundamental Neurosciences, University of Lausanne, CH-1005, Lausanne, Switzerland 2) Centre de Recherche en Neurobiologie et Neurophysiologie de Marseille, Aix-Marseille Université UMR7286 CNRS 13344 Marseille Cedex 15, France 3) Department of Molecular Physiology, University of Saarland, D-66421 Homburg, Germany CMBN, Rikshospitalet 4) Department of Clinical Neurosciences, CHUV, University of Lausanne, Switzerland 5) Neuroscience Research Center, CHUV, CH-1011 Lausanne, Switzerland 6) Department of Psychiatry, Douglas Mental Health University Institute, McGill University, Montreal, Quebec, H4H1R3, Canada 7) NSERM, UMRS 1130; CNRS, UMR 8246; Sorbonne University UPMC, Neuroscience Paris-Seine, F75005, Paris, France CNRS 8) Departments of Neurology and Physiology, University of California San Francisco, San Francisco, California 94158, USA SSN Annual Meeting 1/18/16 5 / 67 Neuromodulation of neuronal circuits of the prefrontal cortex (PFC) by monoamines influences synaptic plasticity and executive functions and may play critical roles in psychiatric disorders (Arnsten et al., 2012). The cellular mechanisms governing the homeostasis of monoamines in the developing PFC are not completely defined. Evidence that astrocytes express the whole enzymatic apparatus for the metabolism of monoamines (Gasser et al., J Neurosci, 2006; Youdim et al., Nature Review Neurosci, 2006) strongly suggests a possible involvement of astroglial cells in mechanisms governing monoaminergic homeostasis. Here we report that astrocytes located in PFC express VMAT2 (Edwards R.H., Neuron, 2007). Immunoperoxidase labeling followed by serial sections analysis and 3D reconstruction show that VMAT2positive astrocytes in PFC contain dopamine (DA) and are strategically positioned between DAergic varicosities and glutamatergic synapses. The physiological relevance of VMAT2 in astrocytes is investigated by generating conditional transgenic mice in which VMAT2 is specifically deleted in GFAP expressing cells (here to referred to as aVMAT2cKO). Interestingly, VMAT2 deletion in astrocytes leads to a specific decrease in the extracellular levels of DA in the PFC. In a different set of experiments, by taking advantage of in vivo microdialysis and of transgenic mice overexpressing Gq protein-coupled receptor (GPCR) Mas-related gene A1 (MrgA1), we directly assess the competence of astrocytes for releasing DA. Finally, we analyse the effects of the decreased levels of DA in the developing PFC in the aVMAT2cKO on spine formation and dendritic growth. To this purpose aVMAT2cKO mice have been crossbreed with Thy1EGFP fluorescent mice (Feng et al., 2000). Taken together, these results highlight a critical role for VMAT2 in astrocytes in the regulation of DA levels and the normal development of pyramidal neurons in the PFC. Integration of grafted neuronal progenitors into the postnatal cerebral cortex. B4 Authors Jevgenia Mihhailova (1), Volodymyr Petrenko (1), Jozsef Zoltan Kiss Affiliations 1) Geneva University, Department of Neurosciences Neuronal death is the key event in the pathogenesis of many neurological disorders. Since postnatal cortex has a limited regenerative capacity, transplantation of neural progenitor cells seems to be the only way to compensate neuronal loss. However, little is known about integration of grafted cells into the host circuits. Here we studied the sequential events that characterize the integration of grafted neuronal precursors in the intact and lesioned neocortex. We utilized a highly efficient diphtheria toxin/diphtheria toxin receptor based model to induce synchronized apoptotic death of the layer II/III neurons in the rat somatosensory cortex at P16 (the period of activity-dependent plasticity). Transplantation of embryonic progenitors was carried 4 days after the lesion followed by the analysis of grafts at days 7, 14 and 30 after transplantation. Our results indicate long survival and good tissue integration of transplanted cells, that typically remain in cluster. Donor cell clusters send out numerous outgrowth to the host tissue and receive innervation from the cortex and thalamus. The layer II/III neurons in cluster are engaged in synaptically interconnected networks (developed dendritic tree, protrusions formation, axonal projections, synaptic contacts with the host layer IV neurons). The lesion environment promotes maturation of transplanted progenitors enhancing the complexity of their dendritic tree and number of dendritic protrusions. Moreover, early transplantation after the lesion as well as intrinsic stimulation of grafted cells improves their integration into the host network. The model provides new possibilities for exploring the integration of transplanted cells into preexisting network following injury. SSN Annual Meeting 1/18/16 6 / 67 Identification of projections from the hypothalamus to the medial and central amygdala nuclei using retrograde tracing with fluorescent beads B5 Authors imane elmghari Affiliations 1) university of Lausanne 2) CHUV The neuropeptide oxytocin (OT) reduces fear responses and plays an important role in social behavior. These functions are mediated by OT receptors (OTR) in resp. the central (CeA) and medial amygdala (MeA). In both nuclei an extensive network of OT fibers can be found that originates from different nuclei in the hypothalamus, namely the Paraventricular (PVN), Accessory (AC) and SupraOptic Nuclei (SON). We here hypothesize that CeA and MeA neurons can be differentially regulated by distinct oxytocinergic projections from the hypothalamus and that an imbalance in OT signaling between the CeA and MeA might underlie certain psychiatric disorders such as autism. To characterize the cellular distribution of neurons projecting from the PVN, we performed a double retrograde labeling by injecting fluorescent latex beads into the MeA and CeA of 28-49 Day old male Sprague Dawley rats. Five days after injection, animals were perfused and coronal slices of the hypothalamus were made of a thickness of 50 micrometers for histological analysis. From a separate group of rats in vitro slices of 400 micrometer thickness were prepared in which fluorescently labeled cells were characterized for their electrophysiological proprieties, using in vitro patch clamp recordings. Our histological results showed the existence of two non-overlapping populations of neurons projecting to the MeA and the CeA from all subdivisions of the PVN (parvocellular or magnocellular cells’ location). Although neurons projecting to the MeA were homogeneously distributed throughout the PVN subdivisions, projections to CeA originated more from the periventricular area, a site where parvocellular neurons are predominantly found. Although whole-cell patch-clamp recordings showed differences in a number of electrophysiological characteristics, notably the input resistance, both populations exhibited electrophysiological characteristics consistent with the parvocellular type. Taken together, our first results provide a first comparative insight in the anatomical-functional organization of oxytocinergic modulation of fear and social neuronal networks, mediated by projections from the PVN to CeA and MeA nuclei. We expect such a specific targeting of the CeA vs MeA with oxytocin will open a new way for therapeutic treatments. C. Molecular and Cellular Mechanisms: Signaling SSN Annual Meeting 1/18/16 7 / 67 Carbonic anhydrase 8 expression in Purkinje cells is controlled by PKC gamma activity and regulates Purkinje cell dendritic growth C2 Authors Etsuko Shimobayashi (1), Josef Kapfhammer (1) Affiliations 1) Anatomical Institute, Deaprtment of Biomedicine, University of Basel, Switzerland Introduction Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant neurodegenerative disorder caused by mutations in the PKC gamma gene. However, it is not well understood how the mutations in the PKC gamma gene lead to Purkinje cell degeneration and dysfunction. Aim The aim of this project is to search the for signalling molecules of mMutant PKC gamma which are related to dendritic growth inhibition of Purkinje cells. Methods In order to search for potential signalling targets of PKC gamma, gene chip assay was performed from the cerebellar slice culture of mutant PKC gamma transgenic mice or control mice. To investigate the function of candidates, we performed immunostaining, WB and gene transfection to dissociated cerebellar culture to observe the morphological change of Purkinje cells. Results We have identified Car8 as a signalling target of PKC gamma which were induced in mutant PKC gamma cerebellum based on the gene chip results as well as Western blotting and immunostaining assay. Car8 overexpression in Purkinje cells also inhibits Purkinje cell dendritic development but miRNA-mediated suppression of CA8 protein does not protect from reduction of dendritic growth by increased activity of PKC. Conclusions Car8 is one of important factor for Purkinje cell dendritic development although Car8 is probably not a direct mediator of PKC gamma for the effects on dendritic growth. Synaptic vesicle exocytosis visualized by cryo-fluorescence and cryo-electron microscopy in millisecond resolution C3 Authors Julika Radecke (1), Harvey McMahon (2), Kenneth Goldie (3), Mikhail Kudryashev (4), Henning Stahlberg (3), Benoît Zuber (1) Affiliations 1) Institute of Anatomy, University of Bern, Baltzerstr. 2, 3012 Bern, CH 2) MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK 3) Biozentrum, University of Basel, Klingelbergstr. 50/70, 4056 Basel, CH 4) Max Planck Institute for Biophysics and BMLS, University of Frankfurt, DE Synaptic vesicle exocytosis, the central event of information processing, learning and memory is important to understand both in health and disease. Exocytosis at the chemical synapse is orchestrated by a pool of ready to release vesicles, containing neurotransmitters for signal transduction. Vesicles are tethered to the active zone by several proteins including synaptotagmin and the SNARE (Soluble NSF Attachment Protein REceptor) fusion machinery. Upon depolarization of the synapse and subsequent transient Ca2+ influx the SNARE complex is remodeled to mediate exocytosis. The remodeling is followed by a hypothesized curvature step of both the active zone plasma membrane and the synaptic vesicle. This curvature step would reduce the energy barrier of the two opposing membranes followed by synaptic vesicle fusion and thereby, neurotransmitter release. SSN Annual Meeting 1/18/16 8 / 67 However, to date the molecular mechanism remains elusive due to the fact that it is a process that can be as fast as 200 μs. To visualize exocytosis we use isolated functional synapses (synaptosomes) that are rapidly frozen milliseconds after depolarization. The synaptosomes are then analyzed by correlative cryo-fluorescence and cryo-electron microscopy followed by 3D reconstruction of the obtained data. Our data indeed show membrane curvature events prior to fusion of the vesicle as well as some potentially short lived states between curvature and fusion and also full-collapse fusion events itself. These events could not be found in control synaptosomes in which synaptic vesicles are tethered to the active zone plasma membrane in their ready to release mode. Based on our ex vivo observations we believe that it will be possible to analyze structural changes of exocytosis and thereby unravel its underlying molecular mechanism to shed electrons on this very fast process. This will improve our general understanding concerning exocytosis to pave the way to further study disease-related processes linked to exocytosis. The gephyrin-interacting protein synArfGEF regulates “mismatched” GABAergic synapses in primary hippocampal neurons C4 Authors Simon Früh (1), Shiva K. Tyagarajan (1), Jean-Marc Fritschy (1) Affiliations 1) Institute of Pharmacology and Toxicology, University of Zurich, Switzerland Postsynaptic differentiation is an important developmental process during synapse formation which is essential for proper synaptic transmission. The accumulation of transmitter-specific receptor, scaffolding and signaling proteins in the postsynaptic density (PSD) depends on transsynaptic signals but is still incompletely understood. In vivo, guidance cues as well as transsynaptic adhesion molecules ensure appropriate postsynaptic differentiation corresponding to the presynaptic terminal. However, the absence of such signaling in dissociated neuronal cultures leads to the formation of mismatched synapses, allowing the study of sorting mechanisms between different types of synapses. The guanine nucleotide exchange factor (GEF) synArfGEF was described to be located in GABAergic synapses, although it was first found in the glutamatergic PSD. We report here that synArfGEF can bind to gephyrin, a postsynaptic scaffolding protein specific to GABAergic (and glycinergic) synapses. Coexpression of tagged synArfGEF and eGFP-gephyrin in rat primary hippocampal neurons lead to accumulation of synArfGEF in the GABAergic PSD. Quantitative cluster analysis revealed that coexpression of synArfGEF caused a decreased density of gephyrin and GABAA receptor clusters not apposed to GABAergic terminals. Conversely, overexpression of a catalytic synArfGEF mutant resulted in an increase of VGluT-apposed gephyrin and GABAA receptor cluster density. No change in apposition of GFP-PSD-95 clusters was detected, arguing that synArfGEF specifically regulates the GABAergic PSD. IQ motif in synArfGEF was required both for reduction of mismatched gephyrin cluster density and for interaction with apocalmodulin. The postsynaptic protein synArfGEF thus regulates GABAergic PSD clustering depending on presynaptic innervation, presumably by activating the small GTPase Arf6. This regulation may be modulated by neuronal activity in glutamatergic synapses as it is dependent on an apocalmodulin-binding motif. Together, our results implicate the postsynaptic protein synArfGEF in differentiation of appropriately matched GABAergic PSDs. Support: UZH-FK grant and SNSF. SSN Annual Meeting 1/18/16 9 / 67 Nogo-A regulates hippocampal CA3 activity by modulating mGlu3 metabotropic glutamate receptors C5 Authors Stewart Berry (1), Oliver Weinmann (1), Ann-Kristina Fritz (2), David Wolfer (2), Martin E Schwab (1, 3), Urs Gerber (1), Jeanne Ster (4) Affiliations 1) Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland 2) InUniversity of Zurich, CH-8057 Zurich, Switzerlandstitute of Anatomy, University of Zurich, CH-8057 Zurich, Switzerland 3) Department of Health Sciences and Technology, ETH Zurich, CH-8057 Zurich, Switzerland 4) Present address: CNRS, UMR-5203; Institut de Génomique Fonctionnelle, INSERM, U1191; Universités de Montpellier 1 & 2, UMR-5203, Montpellier, F-34094, France Recent evidence implicates Nogo-A dysfunction in neuropsychiatric disorders such as schizophrenia. Here we characterized functional roles of Nogo-A within the mouse CA3 hippocampal circuitry. Patch clamp recordings revealed that the absence of Nogo-A results in a hyperactive network. In addition, mGlu3 metabotropic glutamate receptors, which exhibit mutations in certain forms of schizophrenia, were downregulated specifically in the CA3 area. Furthermore, Nogo-A-/mice showed disordered theta oscillations with decreased incidence and frequency as well as a shift in polarity from inhibitory to predominantly excitatory, similar to those observed in mGlu3-/mice. As disruptions in theta rhythmicity are associated with impaired spatial navigation, we tested mice using modified Morris water maze tasks. Mice lacking Nogo-A exhibited altered search strategies, displaying greater dependence on global as opposed to local reference frames. Our evidence for a link between Nogo-A and mGlu3 receptors thus provides a new perspective in the search for mechanisms underlying schizophrenia. Homer1 proteins govern mGluR5-dependent Ca2+ signaling in astrocytes C6 Authors Lara Buscemi (1, 2), Vanessa Ginet (1), Paola Spagnuolo (1), Carlo Sala (3), Anita Truttmann (4), Lorenz Hirt (2), Julien Puyal (1), Paola Bezzi (1) Affiliations 1) Dept of Fundamental Neurosciences, UNIL, Lausanne, Switzerland 2) Dept of Clinical Neurosciences, CHUV, Lausanne, Switzerland 3) Institute of Neuroscience, National Research Council, Milan, Italy 4) Neonatology Service, CHUV, Lausanne, Switzerland Astrocytes sense and transduce neuronal activity through G-protein-coupled receptor (GPCR)-mediated increases in their intracellular Ca2+ concentration. Although astrocytic Ca2+-excitability has been thoroughly described during the last decade, its pathophysiological implications are still poorly understood. It has been recently shown that cultured astrocytes possess functional sub-plasma membrane Ca2+-microdomains that control exocytosis of astrocytic glutamate in response to mGluR5 activation, and that, in dendritic spines, the Homer1b/c scaffold proteins provide a molecular tether between mGluRs on the plasma membrane and IP3Rs on the endoplasmic reticulum and thus regulate Ca2+ signaling. Following these leads, we here investigated whether Homer1 proteins were part of astrocytic sub-membrane Ca2+ microdomains and what could be their role in the regulation of Ca2+ signaling and of astrocytic glutamate release. We found in murine cortical tissue that, in basal conditions, astrocytes express Homer1b/c that partially co-localizes with mGluR5, whereas the levels of Homer1a, a shorter stress-related splice variant that competitively prevents the interaction between mGluRs and IP3Rs, were negligible. Using a rat model of neonatal ischemia we studied the expression of both Homer1 forms in astrocytes under inflammatory conditions. Quantification of Homer1 expression in the ipsilateral cortex at 7 days post-ischemia showed a decrease in Homer1b/c together with an increase in SSN Annual Meeting 1/18/16 10 / 67 Homer1a. Immunofluorescence analysis at this time-point showed that reactive astrocytes expressed high Homer1a levels. We then investigated the functional role of astrocytic Homer1a and we found that it strongly attenuated both mGluR5-evoked Ca2+ mobilization and glutamate release. We thus propose a new and intriguing mechanism by which Ca2+ excitability is regulated in astrocytes via Homer1 proteins affecting the bi-directional glutamatergic communication with neurons. The uncoupling of plasmalemmal glutamate receptors from Ca2+-intracellular signaling could be used as a mechanism to tune down the exacerbated glutamatergic response observed after ischemic insults, thereby protecting the tissue from excessive damage. Supported by grant FN 310030_135617 to LH and PB Cell-to-cell variability in energy metabolism in astrocytes: modulation by glutamatergic signaling C7 Authors Guillaume Azarias (1), Haissa de Castro Abrantes (2), Jean-Yves Chatton (2), Bruno Weber (1) Affiliations 1) Institute of Pharmacology and Toxicology, University of Zurich 2) Department of Fundamental Neurosciences, University of Lausanne Astrocytes are non-neuronal cells tiling the entire central nervous systems. They are vital for neural circuit function but have traditionally been viewed as simple, homogenous cells that serve the same essential supportive roles everywhere. However, astrocytes are subject to intrinsic noise, signaling pathways and control mechanisms leading to a cell-to-cell variability, whose functional relevance poorly remains poorly understood. Recent evidence indicated that single astrocytes release variable concentrations of lactate in response to stimulation, raising the possibility that they have different energy metabolisms. To investigate this hypothesis, we used high-content screening methods to monitor at the single cell level the variability in cellular ATP level in cultured astrocytes. An automated image analysis pipeline enabled the time-resolved quantification of both, the single-cell ATP level and the coefficient of variation in a cellular population. At resting state, astrocytes exhibited a significant variability in cellular ATP levels. As previously reported, glutamate induced a decrease in cellular ATP levels that recovered after stimulation. During the glutamatergic stimulation, the heterogeneity in the cellular ATP level decreased, suggesting that the decrease in cellular energy status is potentially regulated to avoid decreasing below a biological threshold. Interestingly, the cytosolic ATP level increased during recovery to a similar level among cells, independently from their basal cellular ATP which further decreased the heterogeneity in cellular ATP levels after stimulation. Therefore, our results suggest that glutamatergic stimulation decreases the heterogeneity in energy metabolism in astrocytes. We speculate that the change in metabolic heterogeneity aims to prime the population to answer more rapidly a next stimulation challenge. Large-scale transcriptional profiling of chemosensory neurons identifies receptor-ligand pairs in vivo. C8 Authors Benoit von der Weid (1, 3), Daniel Rossier (1, 3), Matti Lindup (1, 3), Joël Tuberosa (1, 3), Alexandre Widmer (1, 3), Julien Dal Col (1, 2), Chenda Kan (1, 3), Alan Carleton (2, 3), Ivan Rodriguez (1, 3) Affiliations 1) Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland. 2) Department of Basic Neurosciences, School of Medicine, University of Geneva, Geneva, Switzerland. 3) Geneva Neuroscience Center, University of Geneva, Geneva, Switzerland. In mammals, olfactory perception is based on the combinatorial activation of G protein–coupled receptors. SSN Annual Meeting 1/18/16 11 / 67 Identifying the full repertoire of receptors activated by a given odorant in vivo, a quest that has been hampered for over 20 years by technical difficulties, would represent an important step in deciphering the rules governing chemoperception. We found that odorants induced a fast and reversible concentration-dependent decrease in the transcription of genes corresponding to activated receptors in intact mice. On the basis of this finding, we developed a large-scale transcriptomic approach to uncover receptor-ligand pairs in vivo. We identified the mouse and rat odorant receptor signatures corresponding to specific odorants. Finally, we found that this approach, which can be used for species for which no genomic sequence is available, is also applicable to non-vertebrate species such as Drosophila. Oxytocin receptor signaling in the prefrontal cortex modulates the inhibition of fear responses by the amygdala. C9 Authors Rodrigo Triana-Del Río (1), Chloé Hegoburu (1), Erwin van den Burg (1), Diego Scheggia (1), Cristian A. Ciobanu (1), Ron Stoop (1) Affiliations 1) CENTRE DE NEUROSCIENCES PSYCHIATRIQUES-CHUV-UNIL LAUSANNE The projections from different areas in the medial prefrontal cortex (mPFC) to the amygdala modulate fear expression and extinction. Dorsally, the prelimbic cortex (PL) projects to the basolateral area of the amygdala (BLA) and facilitates fear expression; ventrally, the infralimbic cortex (IL) projects to the intercalated cell masses (ITC) and promotes fear extinction. Additionally, it has been hypothesized that oxytocin (OT) and its receptor (OTR) modulate those pathways. In the mPFC OTR have been found in somatostatin positive cells, a type of inhibitory cells (IN’s) known to inhibit the dendrites of PN, but also of the parvalbumin positive neurons (PV+), thus, the OTR signalling could be involved in an inhibitory circuit within the mPFC, that modulates the excitatory projections to the amygdala, influenced by the endogenous release of OT in the different areas of the mPFC and the oxytocin signalling performed by its receptor. To elucidate these apparent controversial actions of OT in the mPFC, the current project seeks to depict the mechanisms by which the OT receptor signalling modulates the two convergent pathways that target the amygdala, in order to induce fear expression or extinction. To address this question, we traced the projections form the mPFC (PrL/IL) to various areas in the amygdala (BLA/ITC) by retrograde labelling. At the moment, successful injections of fluorescent beads have been performed in the amygdala, leading to fluorescently labelled cell bodies in the L5 of mPFC; we coupled this tracing technique with patch clamp recordings, in order to identify the sensitivity of amygdala projecting neurons in the mPFC to OTR activation. In patch clamp experiments, we found that OTR activation in BLA projecting cells within the prelimbic cortex (L5) increases inhibitory postsynaptic currents, implying that the OTR signalling could inhibit the excitatory projections from PL to BLA, the triggering pathway for fear expression. Ongoing experiments seek to observe the behavioural effect of OTR blockade during fear expression, extinction, and renewal. Moreover, we are in the process to design an AAV construct that identifies SOM positive cells, which will be used to test electrophysiologically the effect of OT over these inhibitory neurons in the mPFC. D. Molecular and Cellular Mechanisms: Learning and Memory SSN Annual Meeting 1/18/16 12 / 67 Hippocampal somatostatin interneurons control the size of neuronal memory ensembles D1 Authors Stefanelli Thomas (1), Bertollini Cristina (1), Lüscher Christian (1, 2), Muller Dominique (1), Mendez Pablo (1) Affiliations 1) Department of Neurosciences, Faculty of Medicine, University of Geneva Michel-Servet 1, 1211 Geneva-4, Switzerland 2) Service of Neurology, Geneva University Hospital, Perret-Gentil 4, 1211 Geneva-4, Switzerland Hippocampal neurons activated during encoding drive the recall of contextual fear memory. Little is known about how such ensembles emerge during acquisition and eventually form the cellular engram. Manipulating the activity of granule cells (GC) of the dentate gyrus (DG), we reveal a mechanism of lateral inhibition that modulates the size of the cellular engram. GC engage somatostatin positive interneurons that inhibit the dendrites of surrounding GC. Our findings reveal a microcircuit within the DG that controls the size to the cellular engram and the stability of contextual fear memory. Dendritic spike generation at CA3 pyramidal cells triggers LTP at recurrent synapses. D2 Authors Federico Brandalise (1), Stefano Carta (1), Fritjof Helmchen (1), John Lisman (2), Urs Gerber (1) Affiliations 1) University of Zurich 2) Brandeis University Several studies have reported a strong correlation between dendritic NMDA spikes and NMDA receptor-dependent synaptic plasticity (Gambino et al., 2014; Brandalise & Gerber, 2014; Cichon & Gan, 2015). Because pharmacological blockade of NMDA receptors prevents both dendritic calcium transients and synaptic potentiation, it has not been possible to establish whether NMDA spikes alone are sufficient to induce LTP. Using an in vitro approach combining two photon calcium imaging and double patch recording from the soma and the dendrite of hippocampal CA3 pyramidal cells, we show that NMDA spikes trigger branch-specific calcium transients leading to the induction of LTP. When applying a subthreshold timing-dependent protocol in which back-propagating action potentials cannot be elicited, we find that facilitating the generation of NMDA spikes promotes LTP whereas conditions associated with a low probability of NMDA spikes fail to induce synaptic plasticity. Furthermore, an analysis of classical spike-timing-dependent plasticity protocols revealed that LTP is only produced if NMDA spikes are evoked. Under conditions where NMDA spikes are prevented, synaptic plasticity is not induced despite the presence of back-propagating action potentials. These results support a mechanism whereby locally generated NMDA spikes, rather than back-propagating action potentials, are the critical event initiating LTP at excitatory dendritic synapses. Structural and functional changes in male and female serotonin 1a receptor knockout mice D3 Authors Christne Fülling (1), Alexandre Pinault (1), Peggy Mittaud (1), Alessandro Cumbo (1), Julien Ackermann (1), Aouatef Abazza (1), Jing Fan (1), Anita Lüthi (1), Jean-Pierre Hornung (1) Affiliations 1) Department of Fundamental Neurosciences, University of Lausanne, Switzerland SSN Annual Meeting 1/18/16 13 / 67 The serotonin 1a receptor has long been implicated in anxiety and mood disorders as well as cognitive functions in animal models and humans. However, the likelihood to develop a certain metal disorder is strongly dependent on the gender. In this study we used mice to understand to which extend the impact of serotonin 1a receptor deletion is influenced by gender. Focusing on the hippocampus – the region with the highest serotonin 1a receptor expression in the forebrain – we identified increased dendritic arborization and synaptic strength of CA1 pyramidal neurons in the stratum radiatum, but not it the stratum lacunosum moleculare of male serotonin 1a receptor knockout mice. In contrast, female serotonin 1a receptor knockout animals do not show altered arborization in the hippocampus. Concomitantly male serotonin 1a receptor knockout mice are more severely affected by receptor deletion than female mice in tests for anxiety and certain paradigms of fear conditioning. They show increased anxiety-related behavior in the open field and the light dark box and freeze significantly less than female knockout and male and female wild-type animals. Interestingly differences in arborization in male serotonin 1a receptor knockout mice are in line with increased synaptic strength in the stratum radiatum that provide an explanation for reduced freezing behavior in these animals. At the same time, male wild-type mice are the only animals able to distinguish cues in the cue discrimination paradigm. In contrast to the differences seen in arborization this behavior parameter seems to be correlating with survival rates of adult born neurons as male wild-type animals show higher levels of survival than all other animal groups. In conclusion, our study underlines the impact of gender-dependent differences in hippocampal morphology and behavior while offering a starting point for gender-dependent treatment studies. Role of REM sleep and melanin concentrating hormone in the neuroprotection effect of sleep deprivation pre-ischemia preconditioning D4 Authors Pace Marta (1, 2), Claudio Bassetti (1, 3) Affiliations 1) Center for Experimental Neurology (ZEN), Department of Neurology, University Hospital (Inselspital), Bern, Switzerland 2) Graduate School for Cellular and Biomedical Sciences, University of Bern 3) Department of Clinical Research, University of Bern Background: It has been shown that REM sleep reduction in the acute phase after stroke is related to poor outcome. In this study, we used Sleep deprivation (SD) as a form of ischemic preconditioning to investigate the role of REM sleep on ischemia. Moreover, our previous microarray study showed an increase of Melanin Concentrating Hormone (MCH), which is a neuropeptide involved in the regulation of REM sleep performed in SD pre-ischemia animals. The objectives of the study are: firstly, to define the role of REM sleep in functional recovery after ischemia and thus may be used as a prognostic marker. Secondly, whether MCH is associated with the pathophysiology of stroke and with the beneficial effect elicited by SD. Methods: Sprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia without previous SD; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery without SD. Electroencephalogram (EEG) combined with electromyogram (EMG) were recorded to evaluate changes in sleep. The time course of the precursor of MCH (Pmch) and its receptor MCH1 receptor (Mchr1) were performed at 4,12 and 24 hours and 3,4 and 7 days following ischemic surgery in the lesioned and contralateral hemispheres by quantitative Real-time qRT-PCR. The infarct size was assessed by cresyl violet staining. Results: REM sleep was significantly increased in the SD_IS (25%) and SD_Sham (30%) groups until 2 days after SSN Annual Meeting 1/18/16 14 / 67 interventions compared to the baseline and all other groups. Conversely, REM was markedly reduced in the IS group (60%) 24h after interventions, when compared to baseline. Both groups that underwent ischemia (SD_IS and IS) showed a significant increase of Pmch and Mchr1 during the acute phase of stroke (4h to 24h) and in both hemispheres relative to the sham group. Furthermore, Pmch was still increased only in SD_IS after 3 and 5 days and in the lesioned hemisphere. Infarct volume was significantly reduced in SD_IS group compared to IS group at 12h (p= .0013); 5 (p= .0001) and 7 days (p= .0019) after ischemia, no reduction was observed at 24h and 3 days. Conclusion: These results indicate that the increase of REM sleep influences infarct volume positively, suggesting that REM may be clinically used as a prognostic marker to identify a subgroup of patients with different outcomes. Additionally, this is the first study, which observed and associated MCH in ischemic context. Since MCH increases the quantities of REM, it would be interesting to determine if MCH agonists could be useful in the treatment of stroke patients. Optogenetic and electrophysiological dissection of oxytocin in brain circuits underlying social buffering of fear in male rats D5 Authors Chloé Hegoburu (1), Supriya Ghosh (1), Rodrigo Triana del Rio (1), Gion Giobellina (1), Isabel Salgado (1), Christophe Grundschober (2), Ron Stoop (1) Affiliations 1) CHUV, University Hospital of Lausanne, Center for Psychiatric Neurosciences, Laboratory on the Neurobiology of Anxiety and Fear, Prilly, Lausanne 2) Neuroscience Discovery, Roche Pharmaceutical Research & Early Development, Basel Innovation Center In gregarious species, social interaction and communication are essential, not only for cooperation within a group, but also for protection from environmental threats exemplified in a decrease of fear in the presence of a conspecific. One candidate mediator for this social buffering of fear is oxytocin (OT), a hormone important for social behavior. We previously found that external application of OT in the central amygdala (CeA) can significantly reduce expression of fear. We here focus on the understanding of the brain circuits which could mediate the endogenous release of oxytocin, notably the ParaVentricular Nucleus (PVN) of the hypothalamus. We hypothesize that activation of projections from the PVN to the CeA are important for the social buffering of the fear response. To test our hypothesis, we combined in male rats electrophysiological recordings in vivo with optogenetic stimulation in the PVN and CeA and recorded concomitant expression of fear learning, expression and reconsolidation in the presence and absence of a companion rat. We found that the presence of the companion immediately as well as long-lastingly decreased fear expression which was blocked by the local administration of an OT receptor antagonist. Electrophysiological recordings in vivo, in combination with optogenetic activation of OT-ergic neurons in the PVN showed that these behavioral responses were accompanied by changes in the activity of OTergic neurons in the PVN as well as differential neuronal responses in the CeA depending on their sensitivity to OT. These findings aim to provide a first characterization of the OTergic circuits involved in social buffering and may open new ways to develop animal models to study the neural processes that underlie behavioral therapy. SSN Annual Meeting 1/18/16 15 / 67 Quantitative analysis of the structural organization of the monkey entorhinal cortex. D6 Authors Olivia Piguet (1), Loïc J. Chareyron (2), Pamela Banta Lavenex (1), David G. Amaral (3), Pierre Lavenex (1, 2) Affiliations 1) Laboratory for Experimental Research on Behavior, Institute of Psychology, University of Lausanne, Switzerland. 2) Laboratory of Brain and Cognitive Development, Department of Medicine, Center for Cognition, University of Fribourg, Switzerland. 3) Department of Psychiatry and Behavioral Sciences, Center for Neuroscience, California National Primate Research Center, M.I.N.D. Institute, UC Davis, Davis, California, USA. The superficial layers of the entorhinal cortex represent the main entryways for the sensory information processed by the hippocampus, whereas its deep layers provide the main exitways through which processed information is sent back to the neocortex. Interestingly, the number of neurons contributing to these pathways varies between subdivisions of the entorhinal cortex. In Eo, 10% of neurons are in layer II, 74% in layer III and 16% in layers V and VI. In Er, 10% of neurons are in layer II, 55% in layer III, 9% in layer V and 26 % in layer VI. In Ei, 13% of neurons are in layer II, 41% in layer III, 15% in layer V and 31 % in layer VI. In Elr and Elc, 17% of neurons are in layer II, 38% in layer III, 15% in layer V and 30 % in layer VI. In Ec, 15% of neurons are located in layer II, 38% in layer III, 15% in layer V and 32 % in layer VI. In Ecl, 21% of neurons are in layer II, 39% in layer III, 13% in layer V and 27 % in layer VI. These data suggest that (1) the rostral entorhinal cortex might project more heavily to CA1 via projections from layer III neurons; (2) projections from entorhinal cortex layer II neurons to the dentate gyrus might increase from rostral to caudal; (3) the targets of return hippocampal projections within the deep layers of the entorhinal cortex might be more prominent caudally. E. Neural Excitability Synapses: Functional Aspects SHANK3 controls maturation of social reward circuits in the VTA E1 Authors Sebastiano Bariselli (1), Stamatina Tzanoulinou (1), Christelle Glangetas (1, 2), Clement Prévost-Solié (1), Luca Pucci (1), Eoin C. O' Connor, Paola Bezzi (1), Francois Georges (2, 3), Christian Lüscher (4, 5), Camilla Bellone (1) Affiliations 1) Dept. of Basic Neurosciences, University of Lausanne, CH-1005, Lausanne, Switzerland. 2) Centre National de la Recherche Scientifique, Interdisciplinary Institute for Neuroscience, UMR 5297, Bordeaux, France. 3) Université de Bordeaux, Bordeaux, France. 4) Dept. of Basic Neurosciences, Medical Faculty, University of Geneva, CH-1211 Geneva, Switzerland. 5) Clinic of Neurology, Geneva University Hospital, CH-1211 Geneva, Switzerland. Haploinsufficiency of Shank3, which encodes an excitatory synapse scaffolding protein, is the most common monogenic cause of Autism Spectrum Disorders (ASDs). How reduced Shank3 copy number affects neural circuits to generate ASD-related behaviors, including poor social interactions, remains elusive. Since social interactions are rewarding experiences, it has been hypothesized that social reward is processed in the reward system. Here, we tested whether VTA-SHANK3 downregulation affects synaptic maturation and social behavior in mice. To mimic haploinsufficieny, we used shRNA against Shank3 during the postnatal maturation. SHANK3 insufficiency altered excitatory transmission onto DA and putative GABA neurons, bidirectionally changing neuronal activity and impairing social preference. Importantly, optogenetic activation of DA neurons of the VTA SSN Annual Meeting 1/18/16 16 / 67 increased social interaction in VTA-SHANK3 mice, indicating that the activity of DA neurons is sufficient to promote social behaviors. Furthermore a positive allosteric modulator of metabotropic glutamate receptor 1 (mGluR1) administered before the fourth postnatal week rescued synaptic transmission and neuronal activity of DA neurons and was sufficient to restore behavioral deficits into adulthood. Thus, Shank3 haploinsufficiency in the VTA impairs postnatal maturation of VTA neurons and disrupts social motivation, while mGluR1 modulation during the critical period offers a potential ASD treatment strategy. Optogenetic characterization of subicular-thalamic connections: Novel function of limbic TRN in head-direction system? E2 Authors Gil Vantomme (1), Zita Rovó (1), Laura Fernandez (1), Anita Lüthi (1) Affiliations 1) University of Lausanne As part of the limbic system, the anterior thalamic nuclei (ATN) are abundantly and reciprocally connected with the hippocampal formation and have the capacity to shape hippocampal spatial and mnemonic information processing. The thalamic reticular nucleus (TRN) controls thalamus through feedforward inhibition, yet its role in the subicular-thalamic head direction system remains largely unexplored. We used both anatomical and functional techniques to determine the nature of subicular afferents of the TRN. Retrograde and anterograde tracers were injected into the limbic TRN and postsubiculum, respectively, to validate the previously described projections. Channelrhodopsin-expressing viruses were then injected into the postsubicular complex, and in vitro and in vivo electrophysiological recordings combined with optogenetic stimulation (blue laser or LED light sources) were performed 3-4 weeks after injection. Using in vitro acute brain slices, we found that the postsubicular glutamatergic neurons discharge reliably upon optical stimulation and that the limbic TRN and ATN neurons discharge action potentials in a time-locked manner in response to postsubicular afferent activation. Synaptic responses were predominantly (~90%) mediated through AMPAreceptors showing comparatively fast (TRN, half-width ~7 ms) and slow (ATN, half-width ~3 ms) decay kinetics. Furthermore, postsubicular thalamic synaptic transmission showed little paired-pulse plasticity. In vivo, in urethane-anesthetized animals, trains of light stimulation triggered repetitive firing in dorsal TRN neurons. Freely moving in vivo data also showed light stimuluslocked-evoked responses along the postsubicular-thalamic axis. Together, these data identify a faithful information transfer between postsubicular and thalamic circuits, notably including TRN, suggesting a role for feedforward inhibition in head direction control. Extracellular potassium elevation modulates glial glutamate uptake providing presynaptic negative feedback on excitatory neurotransmission E3 Authors Anne-Bérengère Rocher (1), Theresa S. Rimmele (1), Joel Wellbourne-Wood (1), Jean-Yves Chatton (1) Affiliations 1) Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, Switzerland Glutamate is released in the synaptic cleft during neuronal activity and cleared out mainly by Na-dependent glutamate transporters at the astrocyte membrane. Glutamate transporter stoichiometry also includes the exchange with K. Extracellular K ([Kout])significantly increases during the repolarization phase of firing neurons. In this study, we show that K directly modulates the kinetics of glutamate transporters. Altering [Kout] had a strong, immediate, and reversible effect on glutamate transport measured by microspectrofluorimetry in SSN Annual Meeting 1/18/16 17 / 67 primary astrocytes. Low [Kout] enhanced transport activity, whereas high [Kout] markedly diminished glutamate capture. The effect was also observed by measuring glutamate transporter currents in voltage-clamped HEK293 cells expressing GLT-1, and astrocytes in acute mouse brain slices. Several independent studies previously demonstrated that pharmacological inhibition of glial glutamate uptake operated a negative feedback on neuronal transmission by causing extrasynaptic glutamate spillover and subsequent activation of presynaptic neuronal group II mGluRs. We thus tested whether K and its modulatory effects on astrocyte glutamate transport could be the physiological trigger for this feedback mechanism. We found that increasing [Kout] from 3 to 6mM caused a reversible decrease in neuronal mEPSC frequency that was prevented by group II mGluR inhibition using LY-341495. These findings reveal a novel negative feedback cascade linking K elevation, glutamate transporter inhibition, and presynaptic mGluR activation. This mechanism could be fundamental for keeping neuronal activity under control. (Supported by Swiss National Science Foundation grant # 31003A_159513/1) Metabotropic glutamate receptors 4 and 7 modulate synaptic transmission from the thalamus to the lateral amygdala E4 Authors Alexandru Cristian Ciobanu (1), Erwin van den Burg (1), Robert Lutjens (1), Ron Stoop (1) Affiliations 1) Centre for Psychiatric Neuroscience, Department of Psychiatry, Lausanne University Hospital Center (CHUV) Thalamic nuclei project strongly to the lateral amygdala (LA) and these connections are important for fear learning and anxiety. The group III metabotropic receptors 4 (mGluR4) and 7 (mGluR7) are expressed in the LA and KO mice studies showed they are involved in acquisition and extinction of fear. In the present study we aimed to investigate the role of these receptors in thalamo-LA synaptic transmission, which has not been properly assessed due to the lack of specific pharmacological agents. To achieve this, we used two new potent and selective compounds: ADX88178, a positive allosteric modulator for mGluR4 and ADX71743 a negative allosteric modulator for mGluR7. Both of them are brain-penetrant and have been shown to have anxiolytic effects in rodents. We hypothesized that the described anxiolytic effects are mediated by mGluR4 / 7 receptors that affect glutamatergic synaptic inputs from the thalamus to the the LA. To test potential effects of mGluR4 and 7 receptors on this pathway, we conducted whole-cell patch-clamp recordings on pyramidal neurons in the LA and assessed effects of mGluR4 and mGluR7 on spontaneous and evoked thalamic synaptic transmission. ADX88178 decreased (from 0.92 ± 0.15 to 0.6 ± 0.08 Hz) and ADX71743 increased (from 1.45 ± 0.3 to 2.57 ± 0.59 Hz) the frequency of spontaneous excitatory postsynaptic currents (EPSCs). When thalamic inputs were electrically stimulated, similar effects with the spontaneous activity were observed on the evoked EPSCs in neurons from the LA, both during lowand high-frequency stimulation (0.07 Hz and 100 Hz respectively): ADX88178 decreased and ADX71743 increased the amplitude of the evoked responses. Thus synaptic transmission from the thalamus is modulated both during low and highfrequency stimulation. These results show that mGluR4 and mGluR7 are functionally expressed in the LA and they control spontaneous neuronal activity and synaptic transmission from the thalamus. This may explain the anxiolytic effects of ADX88178 and ADX71743 previously observed in systemically treated animals. The fact that at cellular level the two compound show opposite effects, suggest their anxiolytic activity is mediated by two different populations of neurons likely part of separate parallel networks. The effects of the allosteric modulators are in agreement with the presynaptic localization and the described physiological function of the receptors. Our data SSN Annual Meeting 1/18/16 18 / 67 suggest a mechanism trough which mGluR4 and mGluR7 modulate pyramidal neurons in the LA and this may have important implications for fear and anxiety disorders. Characterizing connectivity and signal propagation in the lateral amygdala through local networks E5 Authors Marios Abatis (1), Ruifang Niu (1), Rodrigo Perin (2), Henry Markram (2), Ron Stoop (1) Affiliations 1) Centre de Neurosciences Psychiatriques, CHUV 2) Laboratory of Neural Microcircuitry, BMI, EPFL Fear conditioning combines an unconditioned stimulus with a conditioned stimulus (CS) so that the CS alone can subsequently elicit fear-related responses. While the convergence of signals onto single lateral amygdala (LA) neurons has been extensively studied, little is known about the role of connections between LA neurons in fear memory encoding. We hypothesize that fear signals are re-integrated in the LA through local neuronal assemblies. We used whole-cell patchclamp recordings to simultaneously access up to 12 neurons at a time, with the aim of mapping network topology and studying the LA-to-LA synapse. We recorded from 571 neurons whose connectivity was assessed by delivering, successively, a train of 8 pulses at 20 Hz and monitoring for induced post-synaptic potentials. We observed 2% connectivity, with the chance to observe a connection decreasing with inter-somatic distance. This suggests a "small-world" network organization. In addition, we assessed connectivity among neurons participating in the fear memory trace after a cued fear conditioning protocol. Neuronal memory-recruitment was assessed by quantifying expression of a destabilized GFP (2 hours half-life) under an enhanced Arc promoter (E-SARE) after fear memory testing. We found that recruited neurons had greater connectivity (9 out of possible 246 connections, or 4%), higher excitatory post-synaptic potential (EPSP) amplitude (1.4±0.1 mV) and higher probability to observe an EPSP (0.5±0.04 %) compared to controls (2 %, 0.6±0.1 mV and 0.3±0.03 %, respectively; ±s.e.m.). This suggests that either stronger and more numerous connections enhance local network excitability and favor memory recruitment or that the observed changes result from memory recruitment, to be determined by future experiments. Finally, we followed the spatiotemporal progression of a signal within the LA network. To this end, we monitored the preferred path of a spontaneous epileptogenic signal which spread from caudal to medial to rostral LA with a delay of 68±31ms between caudal and rostral ends. Interestingly, this path coincides with a caudal termination of external capsule fibers in the LA (input) and rostral projections from the LA to the basolateral amygdala (output). Membrane potential dynamics of specific L2/3 and L4 neurons during behavior E6 Authors Taro Kiritani (1), Carl Petersen (1) Affiliations 1) Laboratory of Sensory Processing, Brain Mind Institute, EPFL SSN Annual Meeting 1/18/16 19 / 67 The network operations in the neocortex are mediated by the interactions between diverse neuron types. However, the functional roles of specific neuron types in awake behaving animals are poorly understood. Here, we performed whole cell recordings in the primary somatosensory barrel cortex of awake, head restrained mice under two photon imaging. The membrane potential dynamics of excitatory, parvalubumin (PV), and somatosensory (SOM) neurons in layer 2/3 and layer 4 of the C2 barrel column were recorded while the C2 whisker movement was filmed. During free whisking, the membrane potentials of L2/3 and L4 excitatory neurons were changed only modestly. L2/3 SOM neurons hyperpolarized during whisking, whereas L4 SOM neurons depolarized. The membrane potentials of L2/3 and L4 PV neurons increased slightly. In response to active touch sensation, L4 excitatory neurons received strong and fast EPSPs. In L2/3 and L4 SOM neurons, transient inhibition was often observed on touches, but this was followed by prolonged excitation. These results reveal the cell type and layer specific neuronal computation. Homeostatic control of presynaptic protein degradation and synaptic transmission E7 Authors Corinna Wentzel, Sebastian Sydlik, Martin Müller Affiliations 1) Institute of Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, 8057 Zurich Homeostatic modulation of neurotransmitter stabilizes synaptic transmission, but the underlying molecular signaling pathways are poorly understood. Work in Drosophila has identified some of the first genes that are required for this form of synaptic plasticity. However, it remains completely unknown how the proteins encoded by these genes homeostatically control presynaptic function. Here we define a key role for the presynaptic proteasome in homeostatic modulation of neurotransmitter release. Specifically, we find that the presynaptic proteasome controls presynaptic release and ubiquitinated protein levels on the minute time scale, and that this regulation is required for the acute induction and the sustained expression of homeostatic potentiation of release at the Drosophila neuromuscular junction. Moreover, we provide the first evidence for links between proteasome function, presynaptic calcium dynamics, and the modulation of a low release probability vesicle pool. Finally, proteasome-dependent control of release is disrupted after loss of specific homeostatic plasticity genes, including the schizophrenia-susceptibility gene dysbindin. Together, our data establish that the presynaptic proteasome plays a pivotal role in controlling specific presynaptic mechanisms and molecules during baseline synaptic transmission and homeostatic plasticity. F. Brain Metabolism and Homeostatis Stimulation-induced metabolic modifications in the visual cortex of the Tupaia Belangeri measured by 1H and 13C MRS at 14.1 T F1 Authors Sarah Sonnay (1), Jordan Poirot (2), Nathalie Just (4), Anne-Catherine Clerc (1), Rolf Gruetter (1, 3), Gregor Rainer (2), João M.N. Duarte (1) Affiliations 1) Laboratory of Functional and Metabolic Imaging (LIFMET), EPFL, Lausanne 2) Visual Cognition Laboratory, Department of Medicine, University of Fribourg, Fribourg 3) Department of Radiology, University of Geneva and Lausanne, Geneva Lausanne 4) Department of Clinical Radiology, University Hospital Münster, Germany Brain activity-associated energy requirements are satisfied by the metabolism of oxygen and glucose. While SSN Annual Meeting 1/18/16 20 / 67 magnetic resonance spectroscopy (MRS) at high magnetic field allows to detail metabolic compartmentation in neurons and astrocytes in vivo, the investigation of functional regulation of energy metabolism requires prolonged and continuous somatosensory stimulation paradigms suited to animal models. We developed a visual-stimulation system for functional MRI and MRS experiments at 14.1 T. After BOLD-fMRI characterization of cortical activity elicited by visual stimulation, MRS was performed in the primary visual cortex (V1) of Tupaia Belangeri under light isoflurane anesthesia at rest and during visual stimulation. Visual stimulation was achieved with 2 matrices of 64 LEDs generating lines randomly moving in 8 different directions at 2 temporal frequencies (5-7 Hz). Reproducible and robust BOLD responses were detected in V1, where the volume of interest was placed for MRS. Preliminary results (n=4) indicated that, relative to baseline, cortical stimulation induced a 35% (-0.3 μmol/g) reduction in cortical glucose concentration, accompanied by ~3% (+0.1 μmol/g) lactate increase. Decrease in levels of aspartate (~4%; -0.1 μmol/g) and increase in glutamate (~1%; +0.1 μmol/g) were also observed during stimulation relative to baseline. These results suggest that increased brain activity is associated with stimulation of glycolysis, malateaspartate shuttle, and glutamatergic neurotransmission rates. 13C MRS was performed during [1,6-13C]glucose infusion at rest or stimulation and 13C incorporation into brain amino acids is currently being analyzed with a mathematical model of compartmentalized energy metabolism to quantify the rate of these biochemical pathways in vivo during enhanced cortical activity. G. Cognitive and Behavioral Neuroscience Does my brain want what my eyes like? How food liking influences choice and impacts spatio-temporal brain dynamics of food viewing G2 Authors Marie-Laure Bielser (1), Camille Crézé (2), Micah M. Murray (1, 3), Ulrike Toepel (1) Affiliations 1) The Laboratory for Investigative Neurophysiology (LINE), Departments of Clinical Neurosciences and Radiology CHUV and University of Lausanne, Switzerland 2) Department of Physiology, University of Lausanne 3) EEG Brain Mapping Core, CIBM, Switzerland; 4 Department of Hearing and Speech Sciences, Vanderbilt University, Nashville, TN 37232, USA The influence of valuation on food-related decision-making and their impact on visual food perception remains poorly understood, although being of great interest for body weight management. Our study investigated behavioral aspects and spatio-temporal brain dynamics related to the viewing of pairs of food images in twenty-two normal-weight participants. Participants were asked to rate their liking for each food item (valuation phase) and to further choose between the two alternatives (choice phase). Further, visual evoked potentials (VEPs) were assessed. Behaviorally, highly liked foods were chosen most often, and also rated faster than mildly liked or disliked foods. At the brain level, the level of liking as well as the subsequent choice modulated VEPs as early as 135-180ms after food image onset. Estimation of neural source activity patterns over this time period showed an interaction between liking and choice within the insula, the dorsal frontal and the superior parietal regions. Yet, modulations by liking were apparent only when the viewed food had been chosen over an alternative. Therein, neural responses to disliked foods were found to be stronger than those to food images that were liked more, showing that the spatio-temporal brain dynamics to food viewing are immediately modulated by both the liking of foods and subsequent choices. These valuation and choice processes occur in brain regions involved in salience and reward attribution as well as in decision-making processes, thus likely influencing daily food choices. SSN Annual Meeting 1/18/16 21 / 67 Visual memory profile in 22q11.2 deletion syndrome: discrepancy between the ventral and dorsal streams G3 Authors Mathilde Bostelmann (1), Maude Schneider (1), Maria Carmela Padula (1), Marie Schaer (1, 2), Johanna Maeder (1), Elisa Scariati (1), Bronwyn Glaser (1), Martin Debbané (1, 3), Sarah Menghetti (1), Stephan Eliez (1, 4) Affiliations 1) Office Médico-Pédagogique, Department of Psychiatry, Geneva Faculty of Medicine, 1 rue David Dufour, P.O. Box 50, CH-1211 Geneva, Switzerland 2) Stanford Cognitive and Systems Neuroscience Laboratory, Stanford University, 1070 Arastradero Road, Palo Alto, CA 94304, USA 3) Adolescence Clinical Research Unit, Psychology Faculty, Geneva University, 40 boulevard du Pont d’Arve, CH-1205, Geneva, Switzerland 4) Department of Genetic Medicine and Development, University of Geneva, 1 Rue Michel-Servet, CH-1211, Geneva, Switzerland Children affected by the 22q11.2 deletion syndrome (22q11DS) show a specific neuropsychological profile with strengths and weaknesses in several cognitive domains. Specifically, previous evidence has shown visual memory impairments characterized by better visuo-spatial memory compared to visual-object memory, which may be linked to abnormalities within the cerebral structures related to these functions. The first focus of this study was to investigate visual memory in 22q11DS and identify a specific pattern of impairments. The second goal was to link visual memory alterations with the integrity of underlying brain regions. Finally, since longitudinal development of such functions has been less characterized in 22q11DS, the third aim was study the evolution of visual memory with age. The sample consisted of 71 patients with 22q11DS aged between 9 and 16 years and 68 control individuals. Dependent variables were the types of memory errors (spatial and object errors) made at the Benton Visual Retention Test (BVRT) and specific subtests evaluating object and spatial memory from the Children Memory Scale (CMS). Longitudinal data obtained from a subset of 26 patients and 25 controls were used to investigate the development of these abilities over time. Cross-sectional results showed that patients with 22q11DS are impaired in all visual memory measures, with stronger deficits in visual-object memory, compared to visuo-spatial memory. No correlations between visuospatial or visual-object memory and morphological brain impairments were found. Longitudinal results showed that subjects with 22q11DS at T1 made more object memory errors than spatial memory errors. This difference was no longer significant at T2. This study highlights that 22q11DS individuals showed impairments in visual memory abilities with more pronounced difficulties in processing information related to shape features of visual stimuli. However, this faculty showed an improvement with time due to potential use of compensatory strategies or to possible differential maturation rates of the ventral and the dorsal streams structures. Spatial working memory deficits in aging: Is it that bad? G5 Authors Giuliana Klencklen (1), Pamela Banta Lavenex (1), Catherine Brandner (1), Pierre Lavenex (1) Affiliations 1) Laboratory for Experimental Research on Behavior, Institute of Psychology, University of Lausanne Working memory, the system that keeps limited amounts of information for brief periods of time to guide behavior, is vulnerable to normal aging. However, spatial working memory, essential in daily activities such as learning new routes or driving a car, is thought to be particularly affected in normal aging. Here, we performed an experiment to test the specificity of this purported age-related decline in spatial working memory, in a real-world allocentric spatial memory task. We tested 24 healthy elderly (6575 yrs) and 24 young adults (20-30 yrs) SSN Annual Meeting 1/18/16 22 / 67 in an open-field memory task under different conditions designed to compare four types of memories (spatial working memory, color working memory, spatial reference memory, color reference memory), under different memory loads (one, two or three items to remember). We used two distinct measures to characterize memory performance: the number of correct choices before erring, an estimate of memory capacity; and the number of errorless trials, an estimate of perfect memory. We found: (1) a general decline of memory performance with age, (2) a greater deficit in working memory than reference memory, independently of the type of information, (3), a greater deficit of spatial reference memory than color reference memory, but (4) no evidence that spatial working memory was more affected than color working memory. These results suggest that different types of memory are differentially affected in aging, but that the deficits in memory performance are linked to the representational demands of the task and not to the type of information to be remembered. Visual Reinforcement of perception of illusory rotations during centrifugation: a novel habituation strategy for motion sickness. G6 Authors Giovanni Bertolini (1, 2), Denis Bron (3), Dominik Straumann (1), Timo Frett (2), Ruth Hemmersbach (2) Affiliations 1) Neurology Department, University Hospital Zurich, Swizerland 2) German Aerospace Center (DLR), Cologne, Germany 3) Aeromedical Center, Dübendorf, Switzerland Artificial gravity through centrifugation is currently the only countermeasure providing an “Earth-like” solution to weightless health hazards. Available centrifuges, however, require the subjects to endure high-speed rotations, causing motion sickness. This is due to conflicts between the perceived direction of gravity and the illusory rotations caused by head movements during centrifugation. Existing habituation protocols are based on prolonged exposure to such conflicts. Although they successfully abate motion sickness, they also reduce responses to rotations. This means that the brain fails to learn how to interpret the signals describing self-motion in artificial gravity environment and sacrifices all self-rotation signals to reduce the conflict. We tested a novel habituation protocol that combine visual reinforcement of the illusory rotations to compensate the priority given to gravity in the habituation process. This was achived by having 10 participants performing head movements while rotating on the ESA Human short arm centrifuge and providing a visual optokinetic stimulation confirming the perceived illusory rotations using the Oculus rift virtual reality headset. The current results suggest that the novel protocol leads to the same habituation of normal protocol (10 control subjects) without reducing the reflexive response to rotations as tested by recording the vestibulo-ocular reflex responses. Allocentric spatial learning and memory deficits in Down syndrome. G7 Authors Pamela Banta Lavenex (1), Mathilde Bostelmann (1), Catherine Brandner (1), Floriana Costanzo (2), Emilie Fragnière (1), Giuliana Klencklen (1), Pierre Lavenex (1), Deny Menghini (2), Stefano Vicari (2) Affiliations 1) Laboratory for Experimental Research on Behavior, Institute of Psychology, University of Lausanne, 1005 Lausanne, Switzerland 2) Department of Neuroscience, Bambino Gesù Children’s Hospital, 00165 Rome, Italy Studies have shown that persons with Down Syndrome (DS) exhibit impaired visuoperceptual memory, whereas their visuospatial memory capacities appear comparatively spared. However, most of the evidence concerning SSN Annual Meeting 1/18/16 23 / 67 preserved visuospatial memory comes from tabletop or computerized experiments which are biased towards testing egocentric (viewpoint-dependent) spatial representations. Accordingly, allocentric (viewpoint-independent) spatial learning and memory capacities may not be necessary to perform these tasks. Thus, in order to more fully characterize the spatial capacities of individuals with DS, allocentric processes underlying real-world navigation must also be investigated. We tested 20 participants with DS and 16 mental age-matched, typically developing (TD) children in a real-world, allocentric spatial memory task. We found that although there was significant individual variation, as a group participants with DS performed worse than TD children on all measures of task performance, suggesting persistent and pervasive deficits in hippocampus-dependent memory in DS. Trace conditioning during acute coma and hypothermia G8 Authors Elsa Juan (1, 2), Nathalie Ata Nguepnjo Nguissi (1), Athina Tzovara (6), Dragana Viceic (3), Marco Rusca (4), Mauro Oddo (5), Andrea O. Rossetti (2), Marzia De Lucia (1) Affiliations 1) Laboratoire de Recherche en Neuroimagerie (LREN), Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, CH-1011 Lausanne, Switzerland 2) Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, CH-1011 Lausanne, Switzerland 3) Neurology Service, Hôpital du Valais, CH-1951 Sion, Switzerland; 4 Department of Intensive Care Medicine, Hôpital du Valais, CH-1951 Sion, Switzerland 4) Department of Intensive Care Medicine, Hôpital du Valais, CH-1951 Sion, Switzerland 5) Department of Intensive Care Medicine, Lausanne University Hospital and University of Lausanne, CH1011 Lausanne, Switzerland 6) Department of Psychiatry, Psychotherapy, and Psychosomatics, University of Zurich, CH-8032 Zurich, Switzerland Trace conditioning consists of learning an association between a neutral conditioned stimulus (CS+) and a salient unconditioned stimulus (UCS) separated by a temporal gap. Recent studies reported trace conditioning during deep sleep and in vegetative state patients by showing a transfer of the unconditioned autonomic response to the CS+. However, the neural underpinnings of such an association in the absence of consciousness such as during coma have never been explicitly investigated. In the present study, we recorded the EEG activity of 29 post-anoxic comatose patients while presenting a differential trace conditioning paradigm using neutral tones as CS+ and alerting sounds as UCS. Most patients received therapeutic hypothermia and all were deeply unconscious according to standardized clinical scales. After repeated presentation of the CS+ and UCS couple, learning was assessed by measuring the reactivation of the EEG activity elicited by the UCS in trials where UCS is omitted after CS+ presentation. To this aim, we decoded the EEG activity during UCS omissions based on a statistical model of the EEG activity in response to the UCS. We found a reactivation of the UCS response in absence of stimulation in eight patients, five of them under hypothermia, with a mean decoding of 0.64 ± 0.02 (SEM). Conditioning was temporally specific within trials since the reactivation manifested primarily at the specific latency of UCS presentation and significantly less before or after this period (p < 0.01). Our results show for the first time that trace conditioning may manifests as a reactivation of the EEG activity related to the UCS in the absence of consciousness. SSN Annual Meeting 1/18/16 24 / 67 The impact of chronotypical variations in alertness on the spatial deployment of visual attention and its physiological correlates G9 Authors Rebecca E. Paladini (1), René M. Müri (1, 2), Tobias Nef (1, 3), Fred W. Mast (4), Urs P. Mosimann (1, 5), Dario Cazzoli (1, 3) Affiliations 1) Gerontechnology and Rehabilitation Group, University of Bern, Bern, Switzerland 2) Perception and Eye Movement Laboratory, Departments of Neurology and Clinical Research, University Hospital Inselspital, University of Bern, Bern, Switzerland 3) ARTORG Center for Biomedical Engineering Research, University of Bern, Bern, Switzerland 4) Department of Psychology, University of Bern, Bern, Switzerland 5) University Hospital of Old Age Psychiatry, University of Bern, Bern, Switzerland Attention is a complex cognitive function that is crucial in everyday life. An influential model postulates that non-spatial (e.g., alertness) and spatial aspects of attention are governed by two distinct, yet interacting, cortical networks in the human brain. However, to date, the interactions between non-spatial and spatial attentional aspects are poorly understood. The aim of the present study was to further elucidate these interactions, by manipulating the alertness level in healthy participants, and assessing the impact of this manipulation on spatial attentional aspects both on a behavioural and on a physiological level. Participants’ alertness level was manipulated through the (a)synchronicity between their chronotype and the time of the day. Hence, participants were tested both during their optimal and their non-optimal time of the day. In each session, participants’ alertness level was assessed both subjectively and objectively. On a behavioural level, the spatial deployment of visual attention was assessed by means of a free visual exploration task, with concurrent eye movement recording. On a physiological level, the excitability of the left and the right posterior parietal cortices (PPCs) – two critical nodes of the network governing spatial attention – was directly assessed by means of a transcranial magnetic stimulation (TMS) twin-coil approach. The results of the subjective and the objective alertness tasks showed a significantly decreased level of alertness during the non-optimal compared to the optimal time of the day. Moreover, the spatial deployment of visual attention, in terms of the spatial distribution of visual fixations, differed significantly during these two time points. The results at the non-optimal time of the day were characterised by a rightward shift of the fixation distribution in the central part of the visual exploration field, as well as by a bilateral narrowing in the periphery of the latter. Furthermore, the cortical excitability of both PPCs significantly differed when measured at the two time points, and there were significant correlations between physiological and behavioural measures. The results of the present study show that the manipulation of non-spatial attentional aspects, such as alertness, can affect the spatial deployment of visual attention, and these effects are measurable both on a behavioural and on a physiological level. The results are discussed within the context of current models of visual attention, and possible implications for healthy individuals and clinical populations are considered. Study of the contribution of circulating factors to non-genomic inheritance in mice G10 Authors Gretchen van Steenwyk (1), Lukas von Ziegler (1), Francesca Manuella (1), Ali Jawaid (1), Johannes Bohacek (1), Nicola Zamboni (2), Paolo Nanni (3), Isabelle Mansuy (1) Affiliations 1) Lab of Neuroepigenetics, University/ETH Zurich, Brain Research Institute, Winterthurerstrasse 190, 8057 Zurich, Switzerland 2) Institute of Molecular Systems Biology, ETH Zurich, 8093 Zurich, Switzerland SSN Annual Meeting 1/18/16 25 / 67 3) Functional Genomics Center Zurich (FGCZ), Swiss Federal Institute of Technology Zurich (ETHZ)|University of Zurich (UZH), CH-8057 Zurich, Winterthurerstrasse 190, Switzerland Adverse environmental experiences in early life constitute a major risk factor for the development of neuropsychiatric diseases in adulthood. These diseases are often heritable, and affect people across families. Because they are induced by environmental exposure, they are thought to involve epigenetic factors. Previous work from our laboratory has demonstrated transmission of trauma-induced behavioral, physiological and molecular alterations across generations in mice using an established paradigm of unpredictable maternal separation combined with unpredictable maternal stress (MSUS). The offspring of MSUS fathers have depressive-like behaviors, impaired risk assessment, altered cognitive performance and antisocial behaviors in up to 3 generations. Such transgenerational transmission is accompanied by persistent changes in several nongenetic marks including DNA methylation and non-coding RNAs, in male germ cells. The mechanisms inducing such changes remain unknown. We postulate that they implicate circulating factors released during trauma exposure that can interfere with non-genetic marks in developing germ cells. To identify such potential factors in blood, we use a combined, high-throughput, proteomic and metabolomic approach. Initial results identified several promising factors involved in immune function, metabolism, behavior and gene regulation that are differentially produced in MSUS postnatal mice. Does Heat Smell Bad? Cross-modal expectancy effects between Pain and Disgust G11 Authors Gil Sharvit (1), Corrado Corradi-Dell'Acqua (1), Patrik Vuilleumier (1) Affiliations 1) University of Geneva When we form expectations regarding future events, we become more sensitive in detecting them. For instance, increased pain sensitivity occurs when the intensity of an upcoming stimulus could be predicted. This effect is knowingly mediated by the anterior insula. However, it is still unknown whether expectations of pain trigger a representation of sensory-specific information of the upcoming event or of its aversive-affective (“unpleasant”) consequences, potentially common with other unpleasant situations such as disgust. We used fMRI and compared for the first time expectancy effects of pain and disgust by using different, but equally unpleasant, nociceptive (thermal) and olfactory stimulations. Cues predictive of the unpleasantness (high/low) and the modality (pain/disgust) of upcoming events were shown to participants, who subsequently rated the subjective unpleasantness associated with thermal/olfactory stimuli on a Likert scale. Reminiscently of earlier studies, we found that the same thermal stimuli were perceived as more unpleasant if preceded by cues threatening about high (as opposed to low) pain. A similar expectancy effect was also found in the domain of disgust. Critically, expectancy effects were observed with the inconsistent trials, in which thermal stimuli were preceded by high-disgust cues, or olfactory stimuli were preceded by highpain cues. However, the effects were stronger in the consistent rather than inconsistent settings. Taken together, our results suggest that expectation of an unpleasant event elicits representations of both its modality-specific properties and its aversive consequences. Analysis of the brain signal associated with this task shed light on the neural substrate underlying these representations. SSN Annual Meeting 1/18/16 26 / 67 The role of motor imagery in brain-machine interface control G12 Authors Silvia Marchesotti (1, 3), Michela Bassolino (2), Andrea Serino (1, 2), Hannes Bleuler (3), Olaf Blanke (1, 2) Affiliations 1) Laboratory of Cognitive Neuroscience, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland 2) Center for Neuroprosthetics, EPFL, Lausanne, Switzerland 3) Laboratory of Robotic Systems, EPFL, Lausanne, Switzerland Despite technical advances in brain machine interfaces (BMI), for as-yet unknown reasons the ability to control a BMI remains limited to a subset of users. We investigate whether individual differences in BMI control based on motor imagery (MI) are related to specific cognitive and electrophysiological markers of MI ability. To this aim, we compared behavioral accuracy of MI, subjective kinesthetic and visual feelings during MI and electroencephalographic parameters between highversus low-aptitude BMI users. High-aptitude BMI users showed higher MI accuracy as captured by subjective and behavioral measurements. More specifically, our results indicate a prominent role of kinesthetic rather than visual imagery. In addition, performance from mental chronometry (a measure quantifying the degree to which imagined and executed movements share a similar temporal profile) is able to discriminate lowand high-aptitude BMI users, suggesting that these behavioral measures can be used as a valuable pre-screening tool before recording EEG activity. We also identified enhanced lateralized -band oscillations over sensorimotor cortices during MI in highversus low-aptitude BMI users. These findings reveal that subjective, behavioral, and EEG measurements of MI are intimately linked to BMI control. Thus, we propose that poor BMI control cannot be ascribed only to intrinsic limitations of EEG recordings and that specific questionnaires and mental chronometry can be used as predictors of BMI performance EEG activity. Neural correlates of sensorimotor illusions induced by visuo-proprioceptive and visuomotor signals G13 Authors Michel Akselrod (1, 2), Julio Duenas (1), Roberto Martuzzi (3, 4), James Sulzer (1, 5), Olaf Blanke (3, 4), Roger Gassert (1) Affiliations 1) Rehabilitation Engineering Laboratory, Federal Institute of Technology of Zurich, Zurich, Switzerland 2) Laboratory of Cognitive Neuroscience, Federal Institute of Technology of Lausanne, Lausanne, Switzerland 3) Center for Neuroprosthetics, Federal Institute of Technology of Lausanne, Lausanne, Switzerland 4) Fondation Campus Biotech Geneva, Geneva, Switzerland 5) REWIRE Lab, University of Texas, Austin, USA Bodily self-consciousness (BSC), which includes the feeling that our body belongs to us (sense of body ownership) and that we control the actions of our body (sense of agency), is originated from the integration of congruent sensorimotor signals. Traditionally, BSC has been experimentally manipulated using conflicting visuo-tactile information and previous neuroimaging studies showed that BSC is associated to activity in premotor cortex (PMC) and posterior parietal cortex (PPC). We hypothesized that visuo-proprioceptive and visuo-motor conflicts modulate BSC, similarly to visuo-tactile stimulation. In this study, we developed a novel MR-compatible paradigm combining robotics and virtual reality to investigate the neural correlates of visuo-proprioceptive and visuo-motor conflicts. While subjects performed a pinching action with their right hand, a pinching virtual hand was displayed. We manipulated the visual and SSN Annual Meeting 1/18/16 27 / 67 kinesthetic congruency between one’s own movements and the corresponding sensory feedback in order to study the associated levels of sense of ownership and agency. Following each stimulation period, participants rated their feeling of ownership over the virtual hand and of agency for the virtual movement. Parametric fMRI analysis using subjective ratings as covariates highlighted two partially overlapping fronto-parietal networks associated with the feelings of ownership and agency. In addition, resting-state whole brain functional connectivity of the PMC differed between high and low respondents to BSC manipulation. Our results suggest that robotically-controlled sensorimotor conflicts can experimentally alter sense of body ownership and agency, thus allowing to highlight the neural bases of BSC, as implemented in a fronto-parietal network integrating kinesthetic, visual, and proprioceptive signals. Evidence for psychosocial stress-induced inflammation, altered dopamine status and impaired reward-directed behaviour in mice G14 Authors Giorgio Bergamini (1), Hannes Sigrist (1), Sandra Auer (1), Jonas Mechtersheimer (1), Tobias Suter (2), Boris Ferger (3), Erich Seifritz (4), Christopher Pryce (1) Affiliations 1) Preclinical Laboratory for Translational Research into Affective Disorders Department of Psychiatry Psychotherapy and Psychosomatics Psychiatric Hospital, University of Zurich, Zurich, Switzerland 2) Clinical Immunology, University of Zurich, Zurich, Switzerland 3) CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach, Germany 4) Department of Psychiatry Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland Understanding the aetio-pathophysiology of depression is the route to identification of efficacious anti-depressant strategies. A major theory is that stress-induced inflammation is aetiological in depression and that one of its effects is to alter dopamine signaling leading to symptoms of maladaptive response to punishment and hyposensitivity to reward. Stimulation of the immune system results in a number of behavioural changes which overlap both with those exhibited during infection/sickness and those that constitute symptoms of depression. They are mediated by circuitry to which the basal ganglia and dopamine (DA) function are central, suggesting that changes in the latter underlie the behavioural pathologies. Inflammatory cytokines can act in the brain to affect the monoamine neurotransmitter systems and dopamine signalling in the basal ganglia may be a primary target. It is hypothesized here that psychosocial stress in mice can induce a) peripheral and CNS inflammatory response, b) attenuation of mesolimbic DA signaling and c) changes in reward-directed behaviour. Mice exposed to chronic social defeat (CSD) exhibited peripheral inflammatory responses including splenomegaly accompanied by increased splenic granulocytes, inflammatory monocytes and T helper 17 cells. Immunohistochemical analysis in mesolimbic regions revealed microglia activation in the ventral tegmental area (VTA) in CSD mice. Regarding the effects of CSD on DA signaling, CSD mice showed decreased dopamine turnover (DOPAC/DA) in the nucleus accumbens (NAcc) and a reduced hyper-locomotor activity in response to a DA transporter inhibitor (GBR 12909). The operant behaviour tests, progressive ratio schedule (PRS) and learned non-reward (LNR), were used to assess CSD effects on reward-directed behaviour under demanding conditions. CSD mice obtained less rewards in the PRS test and more errors in the LNR test, compared to controls. Dopamine depletion in the NAcc – achieved using the neurotoxin 6-hydroxydopamine – also induced these operant effects, implicating mesolimbic DA dysfunction in CSD mice. These data support the stress-inflammation-dopamine hypothesis for depression and the model will be utilised to identify novel targets for restoring DA function as an antidepressant treatment. SSN Annual Meeting 1/18/16 28 / 67 Adult neural progenitor cells autotransplantation in a non-human primate model of Parkinson’s disease: a pre-clinical study G15 Authors Simon Badoud (1), Simon Borgognon (1), Jérôme Cottet (1), Pauline Chatagny (1), Véronique Moret (1), Michela Fregosi (1), Jocelyne Bloch (2), Jean-François Brunet (2), Eric Rouiller (1) Affiliations 1) University of Fribourg, Department of Medicine, Switzerland 2) Department of Clinical Neurosciences, Lausanne University Hospital, Switzerland Autologous cells transplantation overcomes several issues raised by the use of human ESC including ethical controversies and immune limitations. The present investigation intended to assess the impact of autologous neural cells ecosystem (ANCE) transplantation in four cynomolgus macaque monkeys exhibiting parkinsonian symptoms. To achieved this goal, monkeys were extensively trained to perform fine manual dexterity tasks as well as a reach and grasp drawer task (Schmidlin et al., 2011) before undergoing systemic MPTP lesions. During the MPTP phase, small cortical biopsies were performed and the gray matter material obtained put into culture according to the protocol developed by Brunet and colleagues (Bloch et al., 2014; Brunet et al., 2002). Additionally, at all phases of the protocol, the integrity of the nigro-striatal system was followed-up by 18F-dopa PET scan. Finally histological analysis allowed determining the fate of the implanted cells and their potential mode of actions. Out of the four animals, two were severely affected by the MPTP lesions whereas the other two exhibited mild symptoms. Furthermore, the 18F-dopa striatal uptake was reduced by about 80% in three of them. Six months following ANCE transplantations, all monkeys presented significant improvement of their motor impairments (spontaneous activity, manual dexterity, posture, etc.). This functional recovery was accompanied by an increase of 18F-dopa striatal uptake. Taken together these new data open new therapeutic perspectives for the ANCE approach regarding neurodegenerative disorders like Parkinson’s diseases. Temporal dynamics of decision making in the Ultimatum Game G16 Authors Sibylle Horat (1), Grégoire Favre (1, 2), Pascal Missonnier (1, 2), Marco Merlo (1) Affiliations 1) Unit of Psychiatric Neuroscience and Psychotherapy, Department of Medicine, Faculty of Science, University of Fribourg, 1700 Fribourg, Switzerland 2) Mental Health Network Fribourg (RFSM), Sector of psychiatry and psychotherapy for adults, 1633 Marsens, Switzerland The behavior of humans in economic decision-making is well established in the literature. The Ultimatum Game (UG) is a typical paradigm to investigate this issue. In the UG, a “Proposer” detains a certain sum of money and is asked to propose a share to the “Responder”. The goal for both is to gain the maximal amount of money by the end of the game. The responder can either accept or reject the offer. If he accepts the proposal the share is done accordingly, whereas if he refuses both players end up with nothing. Although the UG is widely used to assess decision-making, the underlying cognitive processes remain poorly understood. Therefore, we aimed to examine the neuronal bases of the proposer and responder conditions, as well as the deliberative and affective SSN Annual Meeting 1/18/16 29 / 67 aspects of decision-making, by performing event related potentials (ERP), independent component analysis (ICA) and source reconstruction. Three major ERP components, the P2, the feedback-related negativity (FRN) and the late positive component (LPC) were observed in a time range of 150 to 800 ms after stimulus onset at medial electrode sites in both conditions. Interestingly, we identified a negative deflection (N2) in the upward slope of the P2, only detectable in the proposer condition. For the P2, both its amplitude and latency were significantly decreased and delayed, respectively, for the responder condition. In contrast, the FRN showed an increased amplitude and shortened latency for the responder condition. Last, the LPC showed a higher activity for the responder condition. Moreover, ICA showed an independent component (IC) activated in the range of the negative deflection observed in the proposer condition. Although this IC was detectable in both conditions, its variance was 2.5 times higher for the proposer condition, therefore only modifying its P2 ERP morphology. Additionally, the electrical source localization showed higher activity in the orbitofrontal cortex and anterior cingulate cortex (ACC) for the proposer condition in the N2 time-range. Together, our findings indicate that the distinction between your own and the perception of another individual’s choice is based on the engagement of multiple neuronal systems. Yet, the timeline of the involvement of the affective-based ACC activity is the functionally relevant dimension and differs depending on the condition the participant is in (with an earlier activation in the proposer condition), although the goal is the same for both tasks. Finally, the intensity of the activation of neuronal bases for cognitive-based judgements reveals a higher involvement of workload for the responder condition. Comparative study of visual learning in four mammalian species G17 Authors Mohamed Faiz Mohamed Mustafar (1, 2), József Arató (1, 3), Abbas Khani (1), Gregor Rainer (1) Affiliations 1) Visual Cognition Laboratory, Department of Medicine, University of Fribourg, Fribourg, Switzerland 2) Department of Neurosciences, University Sains Malaysia, Kelantan, Malaysia 3) Department of Cognitive Science, Central European University, Budapest, Hungary The study of the neural basis of cognitive processes in animal models often involves the training on specific behavioral tasks. Training protocols are frequently based on operant conditioning procedures and proceed in a step-by-step fashion until the animal has achieved the desired performance on the task at hand. The efficacy with which different mammalian species are able to learn to perform visual tasks is related to their natural tendency to utilize visual information for guiding behavior. To compare learning-related behavioral characteristics among species, they must be trained to perform identical tasks, which has rarely been done up to now. Here, we trained humans, macaque monkeys, tree shrews and rats on a three way alternative choice task. Subjects were trained to discriminate a flickering stimulus (target) from two non-flickering stimuli (distractors). During initial training, the distractors were much less bright than the target (“high hint condition”), and subsequently their brightness was increased in several steps until target and distractors were of equal brightness (“no hint condition”). All animal species acquired the high hint condition quickly, although rats tended to learn slower than tree shrews and macaque monkeys (2.8 vs. 9.8 and 7.5 % correct per day respectively). Learning rate decreased as the hint became smaller for all species. Unlike the two other species, rats had profound difficulty in transferring between more challenging hint conditions. Learning rates tended to be similar in macaques and tree shrews across hint conditions, although monkeys did achieve higher ceiling SSN Annual Meeting 1/18/16 30 / 67 performance levels than rats. The differences in learning dynamics may reflect natural tendencies of each species in terms of visual information use. The greater capacities for visually based behavioral learning reflect the diurnal lifestyle of macaque and tree shrew. Gamma aminobutyric acid receptor antagonist promotes functional neurological recovery after permanent distal middle cerebral artery occlusion in rats G18 Authors Pace Marta (1, 3), Laura Facchin (1, 3), Antoine Adamantidis (1, 2), Patricia Machado (4), Dirk Hermann (5), Claudio Bassetti (1, 2) Affiliations 1) Center for Experimental Neurology (ZEN), Department of Neurology, University Hospital (Inselspital), Bern, Switzerland 2) Department of Clinical Research, University of Bern 3) Graduate School for Cellular and Biomedical Sciences, University of Bern 4) Institut de Recherches Internationales Servier (I.R.I.S.) 5) Department of Neurology, University Hospital, Essen, Germany Background: stroke is one of leading causes of permanent disability, however no treatment is available for promoting recovery. Gamma-aminobutyric acid receptors (GABAAR), responsible for tonic neuronal inhibition, are elevated in the peri-infarct region and may antagonize the neuronal plasticity required for functional recovery after stroke. The objective of the study is to determine the safety and effects on functional recovery after stroke of potent and competitive selective GABAAR antagonists on rats that underwent middle cerebral artery occlusion. Methods: Sprague-Dawley rats, randomly assigned either to sham surgery or permanent distal middle cerebral artery occlusion, were subjected to twice-a-day treatment with the 5GABAAR antagonist S44819, administered at two doses, 3 and 10 mg/kg, respectively, or vehicle. S44819 was orally administered over 28 days starting at day 3 post-stroke. Rats were sacrificed after 2 weeks of washout at day 45 post-stroke. Single pellet reaching (SPR) tests were performed for assessing functional recovery after the stroke at 10, 17, 24, 31, 38 and 45 days post-surgery. Infarct volume was evaluated by cresyl violet staining. Results: Rats receiving 10 mg/kg of S44819 showed a significantly better performance in SPR rests than rats receiving 3 mg/kg of S44819 or vehicle. Notably, functional recovery in rats receiving 10 mg/kg of S44819 was fast, reaching a plateau effect already 10 to 17 days post stroke. Infarct volume did not differ between groups. Conclusion: These results indicate that a high dosage of chronically administered S44819 improves functional neurological recovery post-stroke in rats, suggesting the utility of this GABAAR antagonist for stroke treatment in human patients. The binding problem 2.0: Multisensory interactions reveal mechanisms of category-specific object processing G19 Authors Pawel J. Matusz (1, 2), Antonia Thelen (1, 3), Joseph Nour (1), Jean-Francois Knebel (1, 4), Celine Cappe (5), Micah M. Murray (1, 4) Affiliations 1) The Laboratory for Investigative Neurophysiology (The LINE), University Hospital Centre and University of Lausanne, Switzerland 2) Attention, Brain, and Cognitive Development Group, University of Oxford, UK 3) Vanderbilt University, Nashville, TN, USA, 4) EEG Brain Mapping Core, Center for Biomedical Imaging (CIBM), Lausanne, Switzerland 5) Centre de Recherche Cerveau & Cognition UMR5549, Toulouse, France SSN Annual Meeting 1/18/16 31 / 67 Object recognition is a staple of goal-directed behaviour in real-world environments, but its mechanisms remain unclear. Traditional, unisensory studies revealed that categorical boundaries are an organising principle of how the brain represents objects, but the dynamics whereby these representations are discriminated seem surprisingly slow (~150ms post-stimulus). Real-world environments are multisensory in nature, and the facilitatory influence of multisensory integration on stimulus processing is well-established. However, majority of the multisensory studies focused on one semantic category alone and the few exceptions that contrasted directly responses to different semantic categories failed to find evidence for differential multisensory activity as a function of stimulus category. This leaves unresolved a fundamental question in cognitive sciences: What are the mechanisms whereby information is put together during object category processing in naturalistic environments, where complementary information is typically available across the senses? To address this issue, we recorded 160-channel EEG from 12 participants while they categorised sounds, drawings or auditory-visual pairs of environmental objects in a living/man-made go-nogo task. The benefits of multisensory presentations were measured behaviourally using the inverse efficiency scores (median reaction time divided by percent correct responses), and electrophysiologically – using non-linear brain responses. Behavioural analyses revealed no multisensory benefits, besides overall performance benefits for living objects. Multisensory benefits were, however, observed, when analyses were performed at a subordinate level within the livingobject category (conspecifics, mammals, birds). Only perception of conspecifics showed multisensory facilitation. At the brain level, multisensory interactions differed across both the ordinate as well as subordinate object categories. Interactions in ERP topography occurred early (<100ms post-stimulus) for living but not for man-made (>100ms post-stimulus) multisensory objects. At the same early latency, interactions in ERP strength differed in polarity across conspecifics and non-human mammals; i.e., sub-additive for conspecifics and super-additive for other living objects. First, our results provide empirical evidence that in multisensory environments the identification of conspecifics is more efficient. More generally, we provide the first evidence that object categorization is accomplished faster in multisensory than unisensory environments. This opens an intriguing possibility that in real-world environments object recognition occurs via the fusion of semi-extracted object attributes from each of the senses. Neural correlates of the Feeling of Presence G20 Authors Fosco Bernasconi (1, 2), Marco Solcà (1, 2), Giulio Rognini (1, 2), Olaf Blanke (1, 2) Affiliations 1) Laboratory of Cognitive Neuroscience 2) EPFL 3) Center for Neuroprosthetics The feeling of a presence (FoP), the sensation that somebody is nearby when no one is actually present, is reported mainly by neurological and psychiatric patients but also by healthy individuals facing extreme situations. Recent findings demonstrated that sensorimotor conflicts between upper limb movements and somatosensory feedback on the back may induce FoP in healthy subjects, suggesting that FoP is caused by misperceiving the source and identity of sensorimotor signals of one’s own body. Despite these new insights into the FoP, very little is known about its neural basis. Here we applied the same sensorimotor conflict in healthy volunteers, while brain activity was measured with a 64-channels EEG. We compared the oscillatory power and estimated the inter-site phase clustering by means of the weighted phase-lag index (wPLI), in response to the condition with a sensorimotor conflict with the condition without a sensory motor conflict. Our results indicate a modulation in the alpha frequency band (8-11Hz), over the left frontocentral sensors. The functional connectivity analyses indicated a desynchronization of SSN Annual Meeting 1/18/16 32 / 67 the gamma frequency band (31-45Hz), between somatosensory areas and frontoparietal areas in the condition with sensorimotor conflict. Collectively, these results are providing new insights into the neural correlates of FoP, and indicate the frontoparietal cortex as the critical network associated to it. Interestingly, the involvement of the frontoparietal areas is supported by previous finding from neurological FoP patients, which indicated that the FoP is associated with three distinct brain regions: temporoparietal, insular, and especially with the frontoparietal cortex. The auditory cortex tracks the temporal dynamics of visual speech during silent lip-reading G21 Authors Pierre Mégevand (1, 2), Manuel Mercier (3, 4), David Groppe (1), Charles Schroeder (5, 6), Nima Mesgarani (7), Ashesh Mehta (1) Affiliations 1) Department of Neurosurgery, Hofstra North Shore LIJ School of Medicine, and Feinstein Institute for Medical Research, Manhasset, NY 11030, USA 2) Department of Neurology, Geneva University Hospitals, 1211 Geneva 14, Switzerland 3) Department of Neurology, Montefiore Medical Center, Bronx, NY 10467, USA 4) Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461, USA 5) Cognitive Neuroscience Laboratory, Nathan S. Kline Institute, Orangeburg, NY 10962, USA 6) Department of Neurosurgery, Columbia University, New York, NY 10032, USA 7) Department of Electrical Engineering, Columbia University, New York, NY 10027, USA Human speech is multisensory by nature: our lips, face and body are set into action when we speak; and being able to see our interlocutor complements and enriches our understanding of what is being said. How does visual speech affect the auditory cortex? According to an influential hypothesis, visual speech could induce phase reset of oscillatory activity in auditory cortex, thus modulating its excitability and optimizing the decoding of auditory speech (Schroeder et al., Trends Cogn Sci 2008). To explore this hypothesis, we recorded the responses of human cerebral cortex to naturalistic auditory and visual speech through intracranial EEG electrodes in patients with drug-resistant epilepsy. Electrodes were localized by co-registering preand post-implantation high-resolution MRI and CT scans. Participants watched and heard short (8-12 second) stories whose ending was cut off; after each story, they indicated whether a written word provided an appropriate ending. Each story was repeated several times, allowing us to measure the degree of phase-locking of the intracranial EEG across repeats of the same story (intertrial coherence, ITC) through time-frequency analysis. We defined auditory cortex as those electrodes that showed increased high-gamma power as well as deltaand theta-band phase-locking to auditory speech. We found that auditory cortex displayed significant phase-locking to visual speech (silent lip-reading) between 1 and 6 Hz, without any concomitant increase in power at these frequencies. We also observed a slight increase in high-gamma power. We then cross-correlated the ITC with mouth opening (approximated by the envelope of the auditory speech signal) and found positive correlations at the same frequencies, indicating that phase-locking in auditory cortex reflected specific characteristics of the visual speech signals. We also found a positive correlation between behavioral performance during silent lip-reading and the 1-to-5-Hz ITC to visual speech in auditory cortex. In order to examine how visual speech signals influence the processing of auditory speech, we compared the amount of phase-locking in auditory cortex when perceiving audiovisual vs. auditory speech and found higher phase-locking to audiovisual speech at 4 and 5 Hz. SSN Annual Meeting 1/18/16 33 / 67 Our results indicate that oscillatory activity in auditory cortex reflects the slow dynamics of visual speech during silent lipreading. They support the notion that visual speech gestures influence the oscillations, and hence the response of auditory cortex to speech sounds. More generally, they underscore the possible role of neuronal oscillations in multisensory integration and predictive coding. Phase-coupling between 9-16Hz local field potential bursts in the basal forebrain and visual cortex beta power during NREM sleep G22 Authors Arndt-Lukas Klaaßen (1, 2), Jayakrishnan Harikrishnavilas Nair (1), Björn Rasch (2), Gregor Rainer (1) Affiliations 1) Visual Cognition Laboratory, Department of Medicine, University of Fribourg 2) Cognitive Biopsychology and Methods, Department of Psychology, University of Fribourg Basal forebrain (BF) cholinergic and non-cholinergic neurons innervate the primary visual cortex (V1) and play an important modulating role in arousal, attention, learning and sleep-wake regulation. The brain-state dependent interactions between BF and V1 remain incompletely understood. Here we focus on BF-V1 interplay during sleep, based on data from five rats with implanted bilateral tungsten electrodes for LFP recordings in the basal forebrain (BF) and the visual cortex (V1). We observed frequent bursts of 9-16Hz LFP activity in the BF during NREM sleep periods (mean number per 15s epoch of 0.88 bursts, compared to 0.18 and 0.25 during wake and REM sleep states respectively). The 9-16Hz BF bursts exhibited a peak frequency of 9.5Hz and average duration of about 630ms. Despite the similarity in parameters of the 9-16Hz BF bursts to cortical sleep spindles, the BF bursts appear to be independently generated from cortical sleep spindles, and exhibit little coordination across brain hemispheres. During BF bursts, V1 beta (10-30Hz) power was elevated, and an analysis of the phase relationship revealed significant coupling between 9Hz BF phase and 30Hz V1 LFP amplitude. Our findings suggest that the BF exerts a robust influence on neural activity in visual cortex during NREM sleep, which is mediated by 9-16Hz BF oscillations. The cortical beta LFP modulation may thus reflect functional innervations from BF to V1 related to sleep regulation and possibly cognitive function during NREM sleep. Neural correlates of the face peripersonal space using ultra high-field fMRI. G23 Authors Eva BLONDIAUX GARCIA (1, 2), Petr GRIVAZ (1, 2), Michel AKSELROD (1, 2), Andrea SERINO (1, 2), Olaf BLANKE (1, 2) Affiliations 1) Laboratory of cognitive Neuroscience, EPFL 2) Center for Neuroprosthetics, EPFL This study investigates the neural correlates of the face peripersonal space, i.e., the space where tactile stimulation on the face is integrated with external multisensory signals. We employed a visuo-tactile paradigm during ultra-high field 7T fMRI, whereby 10 participants were presented with a virtual ball looming towards their face, while they received tactile stimuli on their cheeks. The tactile stimuli could occur at different temporal offsets, corresponding to instances when the ball was perceived in near, intermediate or far space. Different premotor and parietal areas showed increasing responses to tactile stimulation, when the ball was close to the face, as compared to farther distances. These results cannot depend just on the distance of the visual stimulus, as no modulation was found in a control condition when only the looming ball was presented. However, many of these areas, with the exception of the cuneus, showed a modulation of activity also in a condition when touch SSN Annual Meeting 1/18/16 34 / 67 was administered while a ball was statically presented in the far space. This pattern of activity might reflect a prediction effect, as if the static ball was perceived as potentially looming. The results of behavioral experiments support this prediction: when the experiment was run in a blocked design, tactile processing was boosted selectively by looming balls in the near space, and not by a far static ball, whereas a mixed design resulted in similar effects for both conditions. These findings support the role of peripersonal space areas in predicting potential contacts. Large-scale sensory integration in the mouse cortex during a tactile detection task. G24 Authors Pierre Le Merre (1, 2), Paul Salin (2), Carl C. H. Petersen (1), Sylvain Crochet (1, 2) Affiliations 1) LSENS, Brain Mind Institute, EPFL, Lausanne 2) FORGETTING team, Lyon Neuroscience Research Center, INSERM/CNRS, Lyon Sensory perception leading to goal-directed behavior involves multiple, spatially-distributed and inter-connected cortical areas. It has been hypothesized that sensory information flows from primary sensory areas encoding mainly the properties of the stimulus, to higher-order, more frontal areas encoding the valence of the stimulus. To understand further the integration of sensory signals, we have recorded sensory evoked potentials (SEPs) simultaneously from different cortical areas in mice performing a whisker-based sensory detection task (Sachidhanandam et al., 2013). Mice were chronically implanted with 6 high-impedance electrodes and were either trained to lick a spout immediately after a 1 ms single whisker deflection to obtain a reward (detection task) or were exposed in the same conditions to the whisker stimulus that was not associated with the reward (neutral exposition). In trained mice, we observed SEPs in all recorded areas with latencies increasing from the barrel-field of the primary somatosensory area (wS1) to the secondary somatosensory area (wS2), the whisker motor area (wM1), the parietal area (PtA), the dorsal hippocampus (dCA1) and the medial prefrontal cortex (mPFC). For each area, we investigated whether the sensory evoked responses correlated with task performance by comparing Hit and Miss trials. We found that the early peak of the SEP differed little between Hit and Miss trials in most areas except for mPFC and dCA1, where SEPs in Miss trials were markedly reduced. Interestingly, SEPs recorded in mice after neutral exposition were also particularly reduced in these areas as compared to trained mice, suggesting that training induced plastic changes in the mPFC and hippocampus leading to increased SEPs in response to the conditioning stimulus. Our results support the idea that mPFC and dCA1 could signal the relevance of a sensory stimulus in the context of a well-defined behavior, whereas sensory areas would be more constrained by the nature of the stimulus. Changing cortisol levels during sleep enhances memory reconsolidation in humans G25 Authors Despina Antypa (1, 2), Ulrike Rimmele (1) Affiliations 1) Department of Neurosciences, University of Geneva 2) Swiss Center of Affective Sciences, Switzerland 3) Lemanic Neuroscience Doctoral School, Switzerland Human episodic memory can undergo changes after reactivation through a process called reconsolidation (for review see Schiller & Phelps, 2011; Nadel et al., 2012; Agren, 2014; Forcato et al., 2014). Changing glucocorticoid levels may be one way of manipulating reconsolidation processes (Coccoz et al., 2011, 2013; Akirav and Maroun, 2012; Dongaonkar et al., 2013; Drexler et al., 2015). Previous human studies point towards SSN Annual Meeting 1/18/16 35 / 67 the possibility that lowering cortisol levels through administration of metyrapone may alter not only retrieval, but possibly also reconsolidation processes (Rimmele et al. 2010, 2015; Marin et al. 2011). In a double-blind,within-subject, counterbalanced design each participant learned two stories in a first session. Two days later, participants were given a reminder cue for one of the stories together with metyrapone vs. placebo. The reactivation was followed by three hours of sleep. Memory for both stories was tested four days later with a recognition test, after metyrapone should be washed out and re-consolidation processes are assumed to be completed. After a period of at least one more week, participants underwent the condition they had not been tested before. The re-activated story followed by cortisol suppression under sleep was remembered better than the re-activated story followed by normal cortisol levels under sleep, while memory performance for the non-reactivated stories did not differ between the metyrapone and placebo condition. These findings suggest that cortisol suppression during sleep can enhance reconsolidation of memories in humans. Optogenetic loss-of-function of cortical motor circuits involved in voluntary action G26 Authors Karin Morandell (1), Gregorio Galinanes (1), Daniel Huber (1) Affiliations 1) Department of Basic Neurosciences, University of Geneva, Switzerland The motor cortex consists of several interconnected subregions playing roles in specific aspects of voluntary movements . A classical approach to attribute function to specific brain areas is local inactivation. However, most silencing techniques are irreversible, invasive or lack the behaviorally relevant time and spatial resolution. In order to overcome these limitations, we developed a non-invasive optogenetic approach to inactivate cortical activity in headfixed mice. We trained mice to discriminate between two vibrotactile stimuli and report their answer by pushing or pulling a joystick after a delay period. Correct answers were rewarded with water. Mice learned the task in 4 to 5 weeks. We tracked forelimb movements and other motor output variables over hundreds of trials per session using automated behavioral control systems and high-speed video recordings. To transiently silence specific motor areas, we used a high resolution optogenetic mapping method. The different motor areas in the contralateral hemisphere were inactivated through the intact skull using a laser scanning system. We found that inactivating forelimb related areas impaired the performance at several levels. The ability to plan the appropriate movement, as well as the execution of forelimb movements were strongly affected when inactivated early or late during the trial, respectively. These results confirm the important role that motor cortex circuits play different aspects of in choice making, planning and execution of goal directed forelimb movements in mice. SSN Annual Meeting 1/18/16 36 / 67 Hemispheric asymmetry in the processing of left/right rotations during spatial updating of scenes. G27 Authors Mitsouko van Assche (1, 2), Valeria Kebets (1, 2), Jonas Richiardi (2), Frédéric Assal (1, 2), Patrik Vuilleumier (2) Affiliations 1) Dpt of Neurology, Geneva University Hospitals, Geneva, Switzerland 2) University of Geneva, Geneva, Switzerland Spatial updating refers to the brain mechanisms that spatially connect our organism with the environment during eye and/or body movements. Visual and posterior parietal areas are implicated in this process (1-4). In the case of guided eye movement, the initial location of a target moving from one hemifield to the other is spatially updated by the ipsilateral brain hemisphere (HMS) (1, 2 5). We studied whether similar mechanisms are at work during the spatial update of scenes under free-viewing conditions, using both univariate and multivariate approaches. We used an fMRI task which simulates head movements by presenting sequences of overlapping viewpoints mimicking leftward or rightward head rotation (6). 4 viewpoints of the same place were presented serially for 2 sec in a specific order, from right to left (RL), or left to right (LR). 2 consecutive viewpoints were shifted by 45° and overlapped by 33%. In theory, in case of LR rotation, information initially located in the right side of the display (i.e., preferentially processed by the contralateral left HMS) moves to the left side during the sequence (i.e., is updated in the ipsilateral right HMS), and vice versa for the RL rotation. In a control condition, the same viewpoint was repeated 4 times (REP). Brain activity was recorded with a 3T MRI, together with high resolution anatomical images. Functional images were preprocessed and analyzed conventionally (SPM8). For univariate analyses, each condition was compared with baseline activity for each subject. The resulting contrast maps were entered into 2nd level models to perform paired t-tests. Multivariate pattern analysis (MVPA) was additionally applied on visual and parietal anatomical regions of interest (left, right and bilateral), using a random forest classifier and a leave-one-subject-per-condition-out cross-validation procedure (in house-built matlab scripts). P values of decoding accuracy were obtained with 1000 permutations. Compared with the REP condition, LR rotations triggered highly right-lateralized activity in visual areas v1 to v4 (p<0.05 FWE corrected), i.e., information updated in the ipsilateral HMS. In marked contrast, the RL condition triggered activity in both left (ipsilateral) and right (contralateral to updated information) visual areas (p<0.05 FWE corrected), suggesting that the right HMS was again implicated in spatial update. When left and right HMS activity was directly compared, the Right>Left HMS comparison showed more activity for both leftward and rightward directions around the parieto-occipital sulcus (p<0.05 FWE corrected). The reverse Left>Right HMS comparison did not reveal significant differences in either rotation direction. In MVPA, there was significant LR vs. RL decoding accuracy in visual areas v2, v3d and v4d (p<0.05). Importantly, rotation direction could be decoded from right HMS in areas v2 (75%) and v3d (68.75%), suggesting that different patterns of activity characterized LR and RL rotations within the same visual areas. Finally in parietal areas, significant decoding accuracies were observed in the intraparietal sulcus, superior and inferior parietal lobules. The data highlight a higher implication of right vs. left occipito-parietal areas for the spatial update of visual scenes under free-