Abstract
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.
Highlights
Determining causal relationships between neuronal circuits and behavior represents a fundamental goal of systems neuroscience
Gene expression was robust and specific to neurons expressing glutamatergic marker α-CamKII (Figure 1B), with 97 % of cells positive for α-CamKII positive for green fluorescent protein (GFP, co-e xpressed with GtACR2), and no neurons (NeuN+, a pan-n euronal nuclear antigen marker) that were negative for α-CamKII and positive for GFP
We identified V1 layers using a standard current-s ink density (CSD) analysis (Hansen et al, 2012) based on the local field potentials recorded in response to a large (5 °) full-contrast dynamic visual stimulus presented for 1600 ms (Figure 2D, see ‘Materials and methods’)
Summary
Determining causal relationships between neuronal circuits and behavior represents a fundamental goal of systems neuroscience. Cortical neurons are embedded in densely interconnected local networks spanning hundreds of microns (Douglas and Martin, 2004; Hirsch and Martinez, 2006; Stettler et al, 2002) These local connections are crucial for contextually modulating neural responses, and they underlie canonical cortical computations such as divisive normalization (Carandini and Heeger, 2011) and surround suppression (Adesnik et al, 2012; Angelucci et al, 2017; Trott and Born, 2015). It is unknown how focal suppression influences activity in the local network (Figure 1A)
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