RT Journal Article SR Electronic T1 All-optical electrophysiology reveals excitation, inhibition, and neuromodulation in cortical layer 1 JF bioRxiv FD Cold Spring Harbor Laboratory SP 614172 DO 10.1101/614172 A1 Linlin Z. Fan A1 Simon Kheifets A1 Urs L. Böhm A1 Kiryl D. Piatkevich A1 Hao Wu A1 Vicente Parot A1 Michael E. Xie A1 Edward S. Boyden A1 Anne E. Takesian A1 Adam E. Cohen YR 2019 UL http://biorxiv.org/content/early/2019/05/23/614172.abstract AB 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.