Nr4a1 regulates inhibitory circuit structure and function in the mouse brain.

Central neurons express unique repertoires of secreted and transmembrane proteins that define their synaptic connectivity. However, how these molecular programs are regulated remains poorly understood. Our study shows that, in inhibitory GABAergic interneurons in the mouse forebrain, transcription of synaptic organizer molecules is controlled by Nr4a1, a nuclear receptor whose expression is transiently induced by sensory experience and required for normal learning. Nr4a1 exserts opposite effects on local axonal wiring of Parvalbumin- and Somatostatin-positive interneurons that innervate different subcellular domains of their postsynaptic partners. Loss of Nr4a1 activity in these interneurons leads to cell-type-specific transcriptional switches in multiple gene families, including those involved in surface adhesion and repulsion. Our findings reveal a mechanism by which inducible transcription factors dynamically alter the combinatorial synaptic organizing codes for structural plasticity.