Astrocytes control the spiking of mouse visual cortex layer 5 pyramidal neurons

Astrocytes are the major glial cell type in central nervous system and vital to support neuronal function network activity. exhibit complex signalling cascades that essential for their normal maintain homeostasis of neural network. Abnormality astrocyte physiology is closely associated with neurological psychiatric diseases, suggesting therapeutic potential these cells. To further understand functions health disease, it important study physiology. Accumulating evidence has shown visual stimulation elicits Ca2+ responses astrocytes (Perea et al. 2014; Sonoda 2018). The linked activities interneurons pyramidal neurons layers 2/3 mouse cortex 2014). Despite wealth literature available on how glia functions, there still substantial gaps our understanding stimulated regulate information processing at cellular level. In a recent article published Journal Physiology, Ryczko (2021) provide activation regulates firing layer 5 (L5PNs) by controlling extracellular levels via releasing binding protein S100β. Previous work demonstrated photostimulation increases excitatory synaptic transmission (V1) study, investigated properties upon proximal astrocytes. L5PNs integrate plethora neocortical inputs along dendritic projections, particular from distal tuft projects branches 1; thus act as source output neocortex other brain regions. Considering significance cortical output, authors planned investigate role L5PNs’ input processing. target photostimulation, first generated GFAP-channelrhodopsin-2 (ChR2)-EYFP mice crossing ChR2-EYFP-lox GFAP-Cre mice. Astrocyte-specific expression fusion ChR2-EYFP GFAP-ChR2-EYFP was validated co-staining EYFP markers (MAP2 NeuN), 94% counted V1 level did not show any signal. assess response ChR2-expressing depolarizations intracellular transients using slices. Successful depolarization (7.3 ± 4.2 mV) increased were evoked combined stimulus 440 488 nm lasers, where optogenetic area restricted 2–3 Upon blue light (i.e. combination lasers) s pulses, displayed an rapid 0.4 141.9 Hz. Next, studied effects applying electrical (1, 5, 10, 20, 30, 40 50 Hz) 1 (L1) axons. Under control conditions, L1 axon elicited both EPSPs spikes most L5PNs; however, maintained throughout higher frequencies such Intriguingly, photostimulated duration number (Fig. 1). particular, optogenetically overrode adaptation frequencies, L5PN continuous spiking during train applied L1. Overall, data showed (440–488 nm) elicit improve Optogenetic induced increase levels, which turn could activate vesicular release gliotransmitters glutamate, GABA, ATP NMDA co-agonist d-serine whether observed be astrocytes, specific pharmacological blockers against AMPA/kainate (CNQX), Glutamate (AP5), GABA (GABAzine), mGluR (LY-341495) purinergic (Suramin) receptors. A reduction range 50% when co-applied CNQX, AP5 GABAzine incomplete block effect antagonists above suggests additional mechanism might involved. decrease concentration intense sustained activity brainstem obtained free S100β (Morquette 2015). episodes Interestingly, reduced 1.24 0.04 1.11 mM compared pre-optogenetic stimulation. Remarkably, time window coincided period astrocyte-evoked spikes. Since modulate persistent sodium current (INaP) dependent 2015), next evoked-spikes rely INaP. Therefore, incubated slices 7–50 min 0.1 μM 4,9-anhydro-tetrodotoxin (4,9-TTX), Nav1.6 α-subunit blocker. They found 4,9-TTX treatment almost removed properties, confirming involvement channels. addressed anti-S100β antibodies bath solution. application μg/ml 8–15 drastically decreased whereas anti-myosin antibody, used no change. Furthermore, (129 μM) or chelator BAPTA (5 mM) 1.2 0.5 mM, respectively, relatively similar those stimulated-astrocytes. By plotting exogenous slices, estimated caused 0.13 corresponding 6.7 6.6 pg This finding serves standard reference future investigations. Similar stimulated-astrocytes L5PNs, L5 resulting whole (0.1 μM, 6–26 min) pre-treated considerably fewer prompting investigation interaction between immunostaining signals adjacent containing fibres, astrocytic sites located close enough locally influence L5PNs. suggest depolarized induces decreases enhances they provided this enhanced channels, either surface charge screening (Frankenhaeuser & Hodgkin, 1957) direct interactions remarkable local occurs noradrenaline arousal, enhance sensory steps will determine recruited vivo, dysfunction translate pathological states. None. All contributed equally. approved final version manuscript agree accountable all aspects work. persons designated qualify authorship, who authorship listed. None would like thank Prof. Dr. Markus Schwaninger Dr Irmgard Dietzel-Meyer valuable while preparing Club article. Further, we also mention due author guidelines able cite deserving references.