Perceptual experiences may arise from neuronal activity patterns in mammalian neocortex. We probed mouse neocortex during visual discrimination using a red-shifted channelrhodopsin (ChRmine, discovered through structure-guided genome mining) alongside multiplexed multiphoton-holography (MultiSLM), achieving control of individually specified neurons spanning large cortical volumes with millisecond precision. Stimulating a critical number of stimulus-orientationselective neurons drove widespread recruitment of functionally related neurons, a process enhanced by (but not requiring) orientation-discrimination task learning. Optogenetic targeting of orientation-selective ensembles elicited correct behavioral discrimination. Cortical layer-specific dynamics were apparent, as emergent neuronal activity asymmetrically propagated from layer 2/3 to layer 5, and smaller layer 5 ensembles were as effective as larger layer 2/3 ensembles in eliciting orientation discrimination behavior. Population dynamics emerging after optogenetic stimulation both correctly predicted behavior and resembled natural internal representations of visual stimuli at cellular resolution over volumes of cortex.
Bibliographical noteFunding Information:
K.D. is supported by the DARPA Neuro-FAST program, NIMH, NIDA, NSF, the Simons Foundation, the Wiegers Family Fund, the Nancy and James Grosfeld Foundation, the H.L. Snyder Medical Foundation, and the Samuel and Betsy Reeves Fund. S.G. was supported by the Burroughs-Wellcome, McKnight, Simons, and James S. McDonnell foundations. J.K. was supported by the Swartz Foundation. This work was also supported by a Simons LSRF fellowship (J.H.M.), the Japan Society for the Promotion of Science (18H04136, S.Y.), a Kwanjeong Fellowship and a Stanford Bio-X fellowship (Y.S.K.), Stanford Dean's fellowships (J.H.M. and T.A.M.), and an AP Giannini fellowship.
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