PT  - JOURNAL ARTICLE
AU  - Vivek Mahadevan
AU  - Apratim Mitra
AU  - Yajun Zhang
AU  - Areg Peltekian
AU  - Ramesh Chittajallu
AU  - Caraoline Esnault
AU  - Dragan Maric
AU  - Christopher Rhodes
AU  - Kenneth A. Pelkey
AU  - Ryan Dale
AU  - Timothy J. Petros
AU  - Chris J. McBain
TI  - NMDAR-mediated transcriptional control of gene expression in the specification of interneuron subtype identity
AID  - 10.1101/2020.06.10.144295
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.06.10.144295
4099  - http://biorxiv.org/content/early/2020/06/12/2020.06.10.144295.short
4100  - http://biorxiv.org/content/early/2020/06/12/2020.06.10.144295.full
AB  - Medial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+ and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical and physiological properties. However, the molecular mechanisms regulating their diversity remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit gene Grin1 mediates subtype-specific transcriptional regulation of gene expression in MGE-derived interneurons, leading to altered subtype identities. Notably, MGE-specific conditional Grin1 loss results in a systemic downregulation of diverse transcriptional, synaptogenic and membrane excitability regulatory programs. These widespread gene expression abnormalities mirror aberrations that are typically associated with neurodevelopmental disorders, particularly schizophrenia. Our study hence provides a road map for the systematic examination of NMDAR signaling in interneuron subtypes, revealing potential MGE-specific genetic targets that could instruct future therapies of psychiatric disorders.Competing Interest StatementThe authors have declared no competing interest.