Dissociation-related behaviors in mice emerge from the inhibition of retrosplenial cortex parvalbumin interneurons.
Cell reports – January 28, 2025
Source: PubMed
Summary
Scientists have pinpointed specific brain cells that control dissociation - a dreamlike mental state where reality feels disconnected. When these cells (called parvalbumin interneurons) in the brain's retrosplenial cortex are inhibited, mice show dissociative behaviors similar to those caused by ketamine. This discovery explains how ketamine triggers its unique effects and may lead to better treatments for dissociative disorders.
Abstract
Dissociation, characterized by altered consciousness and perception, underlies multiple mental disorders, but the specific neuronal subtypes involved remain elusive. In mice, we find that dissociation-inducing doses of ketamine significantly inhibit retrosplenial cortex (RSC) parvalbumin interneurons (PV-INs), enhancing delta oscillations (1-3 Hz) and delta-gamma phase-amplitude coupling (δ-γ PAC) and inducing dissociation-like behaviors. Optogenetic inhibition of RSC PV-INs triggers delta oscillations, δ-γ PAC, and some dissociation-like behaviors without ketamine. Furthermore, activation of RSC PV-INs or knockdown of the N-methyl-D-aspartate receptor subunit NR1 and the hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) in RSC PV-INs attenuates ketamine-induced delta oscillations, δ-γ PAC, and certain dissociation-like behaviors. These findings reveal that PV-INs regulate delta oscillations and δ-γ PAC and identify NR1 and HCN1 as ketamine targets in PV-INs that may cooperatively affect dissociation, possibly providing potential therapeutic targets for dissociative symptoms.