Systematic microcircuit reconfigurations underlie early experience-induced visual cortical plasticity

Summary Experience-dependent reorganization of neuronal connections during a postnatal critical period (CP) is essential for the functional maturation of developing primary visual cortex (V1). However, the systematic reconfigurations across microcircuit synapses underlying this plasticity were poorly defined. Paired recording from excitatory pyramidal cells and other three major interneurons (INs) within layers 2/3 and 4 microcircuits in the developing mouse V1 monocular region, we find that monocular deprivation (MD) for one-day during the CP transiently reconfigures local excitatory synapses on inhibitory INs that specifically express parvalbumin (PV) or vasoactive intestinal peptide (VIP), whereas prolonged MD primarily strengthens inhibitory transmission from somatostatin (SST)-expressing INs to PV-INs and VIP-INs in both layers. A physiologically based microcircuit model suggests these coordinated synaptic changes in specific inhibitory neurons mediate differential MD-induced plasticity in visual responses across layer 2/3 neurons in vivo . Together, our findings define a systematic microcircuit basis for cortical critical-period plasticity. Highlights Inhibitory-to-inhibitory connectivity is conserved in cortical layer 2/3 and 4 circuits. Early experience sequentially modifies excitatory and dis-inhibitory synapses in both layers. Systematic microcircuit reconfigurations underlie plasticity of cortical visual responses. Modeling suggests a pivotal role of disinhibitory microcircuits in mediating the plasticity.