Activity Dependent Regulation of Inhibitory Circuitry
Citation
Sharma, Nikhil. 2015. Activity Dependent Regulation of Inhibitory Circuitry. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences.Abstract
Inhibition controls information flow through a neural circuit by modulating synapticintegration, 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.
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