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 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.

中文翻译：

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行为动物皮质失活的异质性副作用

皮层失活代表了一种关键的因果操作，可以研究皮层回路及其对行为的影响。这些研究中的一个关键假设是目标区域的神经元变得沉默，而周围的皮​​层组织受到的影响可以忽略不计。然而，单个神经元嵌入复杂的局部电路中，该电路由兴奋性和抑制性细胞组成，连接延伸数百微米。这增加了一种可能性，即沉默网络的一部分可能会在目标失活区之外的神经元中引起复杂的、不可预测的活动变化。这些脱靶副作用可能会使灭活操作的解释复杂化，尤其是当它们与行为变化有关时。这里，我们证明了猴 V1 表层谷氨酸能神经元的光遗传学失活会在光靶向位点引起强烈的抑制，但会破坏邻近的非靶向网络中的刺激反应。我们在皮层柱内确定了 4 种刺激诱发的神经元反应，从完全抑制到促进，以及两者的混合。混合反应在中层和深层皮质层最为突出。重要的是，这些结果表明，由横向网络连接驱动的响应调制在整个皮质柱中以不同的方式实现。此外，只有当累积的网络活动被均匀抑制时，才能实现由光遗传学失活引起的一致的行为变化。所以，