Speaker 2: Thomas Klausberger, Austria

I will first introduce the concept of “cognitive-type” cortical microcircuit exemplified by the prefrontal cortex. Since mental disorders primarily implicate cognitive-type brain systems such as the prefrontal cortex, rather than early sensory systems, progress in this area holds the promise for a new approach to psychiatric diagnosis and treatment. I will review experimental and computational research on the generation of brain oscillations during awake, behaving conditions, which depend on various subtypes of interneurons and may serve as endophenotypes for detecting abnormality of GABAergic systems associated with Schizophrenia. However, interneurons are important not only for synchronous rhythms, but also other important functions such as stimulus selectivity of neural populations, winner-take-all competition or normalization. In particular, working memory is a cardinal cognitive function impaired in mental disorders. Interestingly, computational circuit modeling of the prefrontalcortex suggested that working memory deficits in Schizophreniaare manifest not so much in terms of working memory storagebut more in the inability to filter out distractors that are behav-iorally irrelevant, in a specific way that was confirmed by humanstudy. Furthermore, we proposed that this resistance againstdistractors in a working memory circuit depends on severalsubtypes of internruons: soma-targeting interneurons that con-trol the output of excitatory pyramidal cells, dendrite-targetinginterneurons that control the inputs to pyramidal cells, andinterneuron-targeting interneurons that preferentially targetthe dendrite-targeting interneurons. These different interneu-ron types are modulated by dopamine differentially.Finally, I will present our unpublished work on how differenttypes of interneurons can instantiate a gating mechanism uti-lized by the brain to flexibly route information flow to the rightplace at the right time. This long-standing gating problem hasrecently gained urgency with the increased attention to studiesof large-scale global brain connectivity and dynamics and theirimpairments in mentally ill subjects. Our work suggests a novelperspective on GABA signaling impairment in mental disorders.References (1) Wang X-J (2013) The prefrontal cortex as a quintessential“cognitive-type” neural circuit: working memory and deci-sion making. Principles of Frontal Lobe Function, Edited by DTStuss and RT Knight, Second Edition, Cambridge UniversityPress, pp. 226–248.(2) Wang X-J and Krystal J (2014) Computational Psychiatry. Neu-ron, 84, 638–654.(3) Wang X-J (2010) Neurophysiological and computational prin-ciples of cortical rhythms in cognition. Physiological Reviews90, 1195–1268.(4) Buzsáki G and Wang X-J (2012) Mechanisms of gamma oscil-lations. Annual Review Neurosci. 35, 203–225.(5) Murray JD, Anticevic A, Gancsos M, Ichinose M, Corlett PR,Krystal JH, Wang X-J (2014) Linking microcircuit dysfunctionto cognitive impairment: Effects of disinhibition associatedwith schizophrenia in a cortical working memory model. Cer-ebral Cortex, 24, 859–872.(6) Wang X-J, Tegnér J, Constantinidis C and Goldman-Rakic PS(2004) Division of labor among distinct subtypes of inhibitoryneurons in a microcircuit of working memory. Proc Natl AcadSci (USA) 101, 1368–1373.(7) Yang G-Y, Murray J, Wang X-J (2015) Dendritic disinhibitonas a mechanism for pathway-specific gating. Submitted toNature Neuroscience. Speaker 2: Thomas Klausberger, AustriaTitle: Contribution of distinct types of GABAergicinterneuron to working memory and decisionmaking AbstractThe distributed temporal activity in neuronal circuits of the pre-frontal cortex combines emotional information with episodic andspatial memory to guide behavioural action. Single neurons ofoften unknown identity have been shown to exhibit specific fir-ing patterns during spatial navigation and decision-making tasks.The cerebral cortex consists of highly diverse neuronal types withdistinct synaptic connectivity, molecular expression profile andcontribution to network activity. Neurons can be divided into excit-atory pyramidal cells, which use glutamate as a neurotransmitterand give both local and long-range axonal projections, and inhibi-tory interneurons, which are GABAergic and control the activityThe distributed temporal activity in neuronal circuits of the pre-frontal cortex combines emotional information with episodic andspatial memory to guide behavioural action. Single neurons ofoften unknown identity have been shown to exhibit specific fir-ing patterns during spatial navigation and decision-making tasks.The cerebral cortex consists of highly diverse neuronal types withdistinct synaptic connectivity, molecular expression profile andcontribution to network activity. Neurons can be divided into excit-atory pyramidal cells, which use glutamate as a neurotransmitterand give both local and long-range axonal projections, and inhibi-tory interneurons, which are GABAergic and control the activity and timing of pyramidal cells mainly through local axons. Theseneurons can be further subdivided on the basis of their distinctaxo-dendritic arborisations, subcellular post-synaptic targets, andby their differential expression of signalling molecules, includingreceptors, ion channels, neuropeptides, transcription factors andCa2+ binding proteins. We aim to determine how distinct types ofneuron support the executive functions of the prefrontal cortex.We have recorded from identified GABAergic interneuronsand pyramidal cells in the prefrontal cortex of freely-movingrats using the juxtacellular recording and labelling technique.We investigated their contribution to network oscillations and adelayed cue-matching-to-place task involving working memoryand decision making. The neuronal identity was determinedwith post-hoc histochemical analysis.We observed two groups of pyramidal neurons which showedtask-related firing patterns: neurons that represented the futuregoal and neurons that fired preferentially during distinct periodsof the task. These firing patterns were modulated by the activ-ity of distinct types of interneuron. For example, we observedthat the firing of parvalbumin-expressing basket cells displayedstrong modulation according to the task episode. Interestingly,