Complex genetic encoding of experience by NPAS4 resulting in a sophisticated reorganization of inhibition.

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Project Abstract When a mouse explores an enriched environment the pyramidal neurons in the CA1 region of its hippocampus receive excitatory inputs and fire action potentials to encode information about their complex environment. This experience-induced activity results in the expression of the activity dependent transcription factor NPAS4 via de novo transcription and translation, as well as local dendritic translation of preexisting NPAS4 mRNA. This enriched environment induced NPAS4 produces changes in gene expression resulting in a sophisticated reorganization of inhibition across the somato-dendritic axis, with an increase in the number CCK Basket Cell synapses onto the somatic region and a decrease in the number of inhibitory synapses on the radiatum dendrites of NPAS4 expressing cells. This proposal describes experiments designed to determine 1) the genetic identity of the radiatum targeting interneuron type which loses synapses onto NPAS4 expressing cells, and 2) the necessity of dendritic translation of NPAS4 in this sophisticated reorganization. These experiments will provide insight into fundamental biology underlying the complex regulation of inhibitory networks and the role that experience and activity dependent dendritic translation play in this process. Given the known relationships between dysregulation of inhibition, dendritic translation, and a variety of neurological disorders with experience dependent symptomology, this work will aid our understanding of neurological function and dysfunction.