Heterogeneous side-effects of cortical inactivation in behaving animals

Cortical inactivation represents a key causal manipulation that allows the study of cortical circuits and their impact on behavior. A key assumption in these 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 comprised 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 V1 induces robust suppression at the light-targeted site, but destabilizes stimulus responses in the neighboring, untargeted network. We identified 4 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. Importantly, these results demonstrate that response modulation driven by lateral network connectivity is diversely implemented throughout a cortical column. Furthermore, consistent behavioral changes induced by optogenetic inactivation were only a...
Source: eLife - Category: Biomedical Science Tags: Neuroscience Source Type: research