First Author | Picard N | Year | 2019 |
Journal | Mol Psychiatry | Volume | 24 |
Issue | 6 | Pages | 828-838 |
PubMed ID | 30696941 | Mgi Jnum | J:358907 |
Mgi Id | MGI:7783778 | Doi | 10.1038/s41380-018-0341-9 |
Citation | Picard N, et al. (2019) NMDA 2A receptors in parvalbumin cells mediate sex-specific rapid ketamine response on cortical activity. Mol Psychiatry 24(6):828-838 |
abstractText | 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. |