Abstract
Brief (2-3d) monocular deprivation (MD) during the critical period induces a profound loss of responsiveness within layer 4 of primary visual cortex (V1). This has largely been ascribed to long-term depression (LTD) at thalamocortical synapses onto pyramidal neurons, while a contribution from intracortical inhibition has been controversial. Here we used optogenetics to probe feedforward thalamocortical and feedback intracortical excitation-inhibition (E-I) ratios following brief MD. While thalamocortical inputs onto pyramidal neurons were depressed, there was stronger depression onto PV+ interneurons, which shifted the thalamocortical-evoked E-I ratio toward excitation. In contrast, feedback intracortical E-I ratio was shifted toward inhibition, and a computational model of layer 4 demonstrated that these opposing shifts produced an overall suppression of layer 4 excitability. Thus, feedforward and feedback E-I ratios onto the same postsynaptic target can be independently regulated by visual experience, and enhanced feedback inhibition is the primary driving force behind loss of visual responsiveness.