In the course of our studies, we have discovered a novel mechanism that a disinhibitory microcircuit initiates critical period plasticity in visual cortex (Kuhlman et al., 2013 Nature).  Our principal findings are that the restoration of binocular-like excitatory firing rates following monocular deprivation results from a rapid, though transient reduction in the firing rates of fast-spiking, parvalbumin-positive (PV) inhibitory interneurons.  We have determined that this is caused by decreased local excitatory circuit input onto PV interneurons.  Because this biological effect maps to a chemically specific class of inhibitory neuron, this work suggests that drugs targeted to the critical period-regulating neurons can help correct central vision disorders in children who have suffered from amblyopia or early cataracts.

Our recent study (Sun et al., 2016 Neuron) sheds new light on the molecular mechanisms that translate brief sensory deprivation into functional changes in circuit connections.  We show that brief monocular deprivation during the critical period down-regulates NRG1/ErbB4 signaling in PV neurons, causing retraction of excitatory inputs to PV neurons.  Exogenous NRG1 rapidly restores excitatory inputs onto deprived PV cells.  PKC-dependent activation and AMPA receptor exocytosis is downstream from the NRG1/ErbB4 signaling event, thus mediating the enhanced PV neuronal inhibition to excitatory neurons.  NRG1 treatment prevents the loss of deprived eye visual cortical responsiveness in vivo.  Our work suggests that therapeutic intervention of NRG1/ErbB4 signaling can likely be developed to help treat central vision disorders in children such as amblyopia, as well as other critical period disorders.