한빛사논문
James H. Marshel1,*, Yoon Seok Kim2,*, Timothy A. Machado1,2,*, Sean Quirin1,*, Brandon Benson3, Jonathan Kadmon3, Cephra Raja2, Adelaida Chibukhchyan2, Charu Ramakrishnan2, Masatoshi Inoue2, Janelle C. Shane4, Douglas J. McKnight4, Susumu Yoshizawa5, Hideaki E. Kato6, Surya Ganguli3, Karl Deisseroth1,2,7,8,†
1CNC Department, Stanford University, Stanford, CA 94305, USA.
2Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.
3Department of Applied Physics, Stanford University, Stanford, CA 94305, USA.
4Boulder Nonlinear Systems, Lafayette, CO 80026, USA.
5Department of Natural Environmental Studies, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa 277-8564, Japan.
6Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, USA.
7Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
8Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
†Corresponding author.
*These authors contributed equally to this work.
Abstract
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-orientation-selective 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.
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