Activity Dependent Regulation of Inhibitory Circuitry

Abstract

Inhibition controls information flow through a neural circuit by modulating synaptic integration, restricting action potentials, and coordinating the activity of ensembles of neurons. These functions are mediated by a diverse array of inhibitory neuron subtypes that synapse on defined domains of a postsynaptic neuron. Activity-dependent transcription controls inhibitory synapse number and function, but how this transcription program affects the inhibitory inputs that form on distinct domains of a neuron remains unclear. We find that behaviorally-driven expression of the transcription factor NPAS4 orchestrates the redistribution of inhibitory synapses made onto a pyramidal neuron, simultaneously promoting inhibitory synapse formation onto the cell body while destabilizing inhibitory synapses formed on the dendrites. This rearrangement of inhibition across a neuron is mediated in part by the NPAS4 target gene brain derived neurotrophic factor (BDNF), which specifically regulates somatic inhibition. These findings suggest that sensory stimuli, by inducing NPAS4 and its target genes, differentially control spatial features of neuronal inhibition in a way that restricts the output of the neuron while creating a dendritic environment that is permissive for plasticity.