Adolescent ketamine exposure impairs spike timing-dependent plasticity and GABAergic transmission in pyramidal neurons of the mouse prefrontal cortex.
The Journal of physiology June 1, 2026 Felipe Guiffa-Gómez, Sashá Van Buuren, Freddy Aguilar et al. 1 citation
Adolescent mice given ketamine, which blocks NMDA receptors, showed lasting deficits in GABAergic inhibition in the medial prefrontal cortex as adults. Recordings from pyramidal neurons revealed reduced spontaneous and miniature inhibitory currents and altered paired-pulse ratios, indicating impaired presynaptic GABA release and diminished function of parvalbumin-positive interneurons. Spike-timing-dependent plasticity was also disrupted: spike pairings that normally cause depression instead induced potentiation. These results suggest that NMDA receptor hypofunction during adolescence produces enduring impairments in inhibitory transmission and shifts plasticity rules, providing mechanistic insight into circuit dysfunction relevant to neurodevelopmental disorders.