Spike-Timing Dependent Plasticity of Inhibition Gates Critical Period Remodeling in Auditory Cortex

Abstract

In auditory cortex, sensory experience during a critical developmental period leads to remodeling of sound frequency representation. Parvalbumin-expressing interneurons (PV-INs) mediate feedforward inhibition in thalamocortical circuits; a disinhibition at the output synapses of PV-INs might be a prerequisite for critical period plasticity. Here, we find a marked spike-timing dependent plasticity at the synapses between PVINs and principal neurons in the input layer of auditory cortex. Long-term potentiation of inhibition (iLTP) is observed upon postsynaptic (principal neuron) then presynaptic (PV-IN) AP firing. The opposite AP sequence causes GABAB mediated long-term depression of inhibition (iLTD), which, upon further development, is converted to iLTP in an experiencedependent manner. Genetic deletion of GABAB receptors in principal neurons converts iLTD to iLTP, and causes profound deficits in critical period plasticity. Thus, in the auditory cortex of young mice, GABAB signaling in principal neurons enforces iLTD at PV-IN output synapses, thereby gating critical period plasticity.