Dissociation-related behaviors in mice emerge from the inhibition of retrosplenial cortex parvalbumin interneurons.
Yue Hu, Yifan Feng, Huoqing Luo, Xiao-Na Zhu, Siyu Chen, Kexin Yang, Ziqing Deng, Mengqiang Luo, Wenjie Du, Qi Wang, Shubai Wang, Kai Wei, Ji Hu, Yingwei Wang
Cell Reports January 28, 2025 DOI: 10.1016/j.celrep.2024.115086 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | Ketamine optogenetic inhibition of RSC PV-INs |
| Topics | Ketamine |
| Keywords | Cp: neuroscience Dissociation Parvalbumin interneurons Phase-amplitude coupling Retrosplenial cortex Dissociative disorders Brain research Psychopharmacology Mental health |
| Citations | 6 |
| Key findings | Ketamine inhibits retrosplenial cortex parvalbumin interneurons, enhancing delta oscillations and delta-gamma phase-amplitude coupling, which drives dissociation-like behaviors in mice; NR1 and HCN1 in these neurons are identified as ketamine targets that may cooperatively affect dissociation. |
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 5
- Cortical Mechanisms Contributing to Ketamine-Induced Dissociation The Neuroscientist December 26, 2025
- NMDA receptor antagonist induced c-Fos expression in the medial entorhinal cortex during postnatal development. Frontiers in Neural Circuits 2025
- A circuit dissection of perception-action decoupling in S-ketamine-induced hallucination-like states. Molecular Psychiatry September 19, 2026
- Cellular and Microcircuit Mechanisms of Anesthetic Disruption of Conscious-State Organization. Cells August 18, 2026
- Ketamine Across the Dose-State Continuum: EEG Signatures, Network Dynamics, and Implications for Brain-State Monitoring in Anesthesia and Critical Care. Brain Sciences August 9, 2026
Cites 5
- Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Archives of General Psychiatry March 1, 1994
- GABA interneurons are the cellular trigger for ketamine's rapid antidepressant actions. Journal of Clinical Investigation November 19, 2019
- Deep posteromedial cortical rhythm in dissociation Nature September 16, 2020
- Characterizing brain dynamics during ketamine-induced dissociation and subsequent interactions with propofol using human intracranial neurophysiology Nature Communications March 29, 2023
- Causal evidence for the processing of bodily self in the anterior precuneus. Neuron August 16, 2023