Heterogeneous side effects of cortical inactivation in behaving animals

eLife

John L Spudich¹  Xiaoqin Liu²  Ariana R Andrei²  Samantha Debes²  Mircea Chelaru²  Roger Janz²  Valentin Dragoi²  Elsa Rodarte³ 

[1] Center for Membrane Biology, Department of Biochemistry and Molecular Biology, McGovern Medical School, University of Texas, Houston, United States;Department of Neurobiology and Anatomy, McGovern Medical School, University of Texas, Houston, United States;Department of Neurology, McGovern Medical School, University of Texas, Houston, United States;

关键词: visual cortex;    optogenetics;    computation;    monkey;    electrophysiology;    behavior;    Rhesus macaque;   

DOI  :  10.7554/eLife.66400

来源: eLife Sciences Publications, Ltd

【 摘 要 】

Cortical inactivation represents a key causal manipulation allowing the study of cortical circuits and their impact on behavior. A key assumption in inactivation studies is that the neurons in the target area become silent while the surrounding cortical tissue is only negligibly impacted. However, individual neurons are embedded in complex local circuits composed of excitatory and inhibitory cells with connections extending hundreds of microns. This raises the possibility that silencing one part of the network could induce complex, unpredictable activity changes in neurons outside the targeted inactivation zone. These off-target side effects can potentially complicate interpretations of inactivation manipulations, especially when they are related to changes in behavior. Here, we demonstrate that optogenetic inactivation of glutamatergic neurons in the superficial layers of monkey primary visual cortex (V1) induces robust suppression at the light-targeted site, but destabilizes stimulus responses in the neighboring, untargeted network. We identified four types of stimulus-evoked neuronal responses within a cortical column, ranging from full suppression to facilitation, and a mixture of both. Mixed responses were most prominent in middle and deep cortical layers. These results demonstrate that response modulation driven by lateral network connectivity is diversely implemented throughout a cortical column. Importantly, consistent behavioral changes induced by optogenetic inactivation were only achieved when cumulative network activity was homogeneously suppressed. Therefore, careful consideration of the full range of network changes outside the inactivated cortical region is required, as heterogeneous side effects can confound interpretation of inactivation experiments.

【 授权许可】

CC BY