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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2018,3,27]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Ketamine is an NMDA receptor (NMDAR) antagonist that alleviates depressive symptoms in patients with treatment-resistant depression within hours of administering a single dose. However, psychoactive side effects limit its use. Understanding the mechanism underlying ketamine\u2019s antidepressant effect is crucial in identifying targets for novel therapeutics with fewer side effects. Here, we report ketamine enhances excitability of pyramidal cells indirectly by reducing synaptic GABAergic inhibition, thus causing disinhibition. Additionally, we investigated whether other NMDAR antagonists and the muscarinic acetylcholine receptor antagonist scopolamine shared this disinhibition mechanism. 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