NMDA 2A Receptors in Parvalbumin Cells Mediate Sex-specific Rapid Ketamine Response on Cortical Activity

Overview

Journal Mol Psychiatry

Specialties Molecular Biology
Psychiatry

Date 2019 Jan 31

PMID 30696941

Citations 30

Authors

Nathalie Picard

Anne E Takesian

Michela Fagiolini

Takao K Hensch

Affiliations

Soon will be listed here.

Abstract

Ketamine has emerged as a widespread treatment for a variety of psychiatric disorders when used at sub-anesthetic doses, but the neural mechanisms underlying its acute action remain unclear. Here, we identified NMDA receptors containing the 2A subunit (GluN2A) on parvalbumin (PV)-expressing inhibitory interneurons as a pivotal target of low-dose ketamine. Genetically deleting GluN2A receptors globally or selectively from PV interneurons abolished the rapid enhancement of visual cortical responses and gamma-band oscillations by ketamine. Moreover, during the follicular phase of the estrous cycle in female mice, the ketamine response was transiently attenuated along with a concomitant decrease of grin2A mRNA expression within PV interneurons. Thus, GluN2A receptors on PV interneurons mediate the immediate actions of low-dose ketamine treatment, and fluctuations in receptor expression across the estrous cycle may underlie sex-differences in drug efficacy.

Citing Articles

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