Neuropil aggrecan, not perineuronal nets, closes the critical period for visual plasticity

Perineuronal nets (PNNs) are widely reported to close developmental critical periods and restrict experience-dependent plasticity. Here we tested this model by selectively eliminating gene expression for aggrecan (Acan), an essential component of PNNs. In visual cortex, PNNs predominantly ensheath parvalbumin-positive (PV+) interneurons. Deletion of Acan in inhibitory neurons eliminated PNNs but did not prevent closure of the critical period. By comparison, deletion of Acan in all neurons, or only in excitatory forebrain neurons, sustained critical-period plasticity in adult mice. Visual plasticity in adults was associated with reduced cortical excitatory synaptic inputs onto layer 2/3 PV+ interneurons and increased expression of some immediate early genes in visual cortex but normal response strength and tuning properties of layer 2/3 excitatory neurons. These findings rectify long-standing models that misattribute closure of the critical period to PNNs and identify that aggrecan expressed by excitatory neurons resident in the surrounding neuropil limits visual plasticity.