NPAS1 Represses the Generation of Specific Subtypes of Cortical Interneurons

Amelia Stanco, Ramón Pla, Daniel Vogt, Yiran Chen, Shyamali Mandal, Jamie Walker, Robert F. Hunt, Susan Lindtner, Carolyn A. Erdman, Andrew A. Pieper, Steven P. Hamilton, Duan Xu, Scott C. Baraban, John L.R. Rubenstein

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Little is known about genetic mechanisms that regulate the ratio of cortical excitatory and inhibitory neurons. We show that NPAS1 and NPAS3 transcription factors (TFs) are expressed in progenitor domains ofthe mouse basal ganglia (subpallium, MGE, and CGE). NPAS1-/- mutants had increased proliferation, ERK signaling, and expression of Arx in the MGE and CGE. NPAS1-/- mutants also had increased neocortical inhibition (sIPSC and mIPSC) and generated an excess of somatostatin+ (SST) (MGE-derived) and vasoactive intestinal polypeptide+ (VIP) (CGE-derived) neocortical interneurons, but had a normal density of parvalbumin+ (PV) (MGE-derived) interneurons. In contrast, NPAS3-/- mutants showed decreased proliferation and ERK signaling in progenitors of the ganglionic eminences and had fewer SST+ and VIP+ interneurons. NPAS1 repressed activity of an Arx enhancer, and Arx overexpression resulted in increased proliferation of CGE progenitors. These results provide insights into genetic regulation of cortical interneuron numbers and cortical inhibitory tone.

Original languageEnglish (US)
Pages (from-to)940-953
Number of pages14
JournalNeuron
Volume84
Issue number5
DOIs
StatePublished - Dec 3 2014
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Stanco, A., Pla, R., Vogt, D., Chen, Y., Mandal, S., Walker, J., Hunt, R. F., Lindtner, S., Erdman, C. A., Pieper, A. A., Hamilton, S. P., Xu, D., Baraban, S. C., & Rubenstein, J. L. R. (2014). NPAS1 Represses the Generation of Specific Subtypes of Cortical Interneurons. Neuron, 84(5), 940-953. https://doi.org/10.1016/j.neuron.2014.10.040