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Publication : Nr4a1 regulates cell-specific transcriptional programs in inhibitory GABAergic interneurons.

First Author  Huang M Year  2024
Journal  Neuron Volume  112
Issue  12 Pages  2031-2044.e7
PubMed ID  38754414 Mgi Jnum  J:349433
Mgi Id  MGI:7646792 Doi  10.1016/j.neuron.2024.03.018
Citation  Huang M, et al. (2024) Nr4a1 regulates cell-specific transcriptional programs in inhibitory GABAergic interneurons. Neuron
abstractText  The patterns of synaptic connectivity and physiological properties of diverse neuron types are shaped by distinct gene sets. Our study demonstrates that, in the mouse forebrain, the transcriptional profiles of inhibitory GABAergic interneurons are regulated by Nr4a1, an orphan nuclear receptor whose expression is transiently induced by sensory experiences and is required for normal learning. Nr4a1 exerts contrasting effects on the local axonal wiring of parvalbumin- and somatostatin-positive interneurons, which innervate different subcellular domains of their postsynaptic partners. The loss of Nr4a1 activity in these interneurons results in bidirectional, cell-type-specific transcriptional switches across multiple gene families, including those involved in surface adhesion and repulsion. Our findings reveal that combinatorial synaptic organizing codes are surprisingly flexible and highlight a mechanism by which inducible transcription factors can influence neural circuit structure and function.
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