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All-optical electrophysiology reveals excitation, inhibition, and neuromodulation in cortical layer 1

By Linlin Z. Fan, Simon Kheifets, Urs L. Böhm, Kiryl D Piatkevich, Hao Wu, Vicente Parot, Michael E. Xie, Ed Boyden, Anne E. Takesian, Adam E. Cohen

Posted 23 Apr 2019
bioRxiv DOI: 10.1101/614172 (published DOI: 10.1016/j.cell.2020.01.001)

The stability of neural dynamics arises through a tight coupling of excitatory (E) and inhibitory (I) signals. Genetically encoded voltage indicators (GEVIs) can report both spikes and subthreshold dynamics in vivo , but voltage only reveals the combined effects of E and I synaptic inputs, not their separate contributions individually. Here we combine optical recording of membrane voltage with simultaneous optogenetic manipulation to probe E and I individually in barrel cortex Layer 1 (L1) neurons in awake mice. Our studies reveal how the L1 microcircuit integrates thalamocortical excitation, lateral inhibition and top-down neuromodulatory inputs. We develop a simple computational model of the L1 microcircuit which captures the main features of our data. Together, these results suggest a model for computation in L1 interneurons consistent with their hypothesized role in attentional gating of the underlying cortex. Our results demonstrate that all-optical electrophysiology can reveal basic principles of neural circuit function in vivo . One Sentence Summary All-optical electrophysiology revealed the function in awake mice of an inhibitory microcircuit in barrel cortex Layer 1.

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