eLife
March 21, 2024
Yue Hu, Wenjie Du, Jiangtao Qi et al.
27 citations
Ketamine and isoflurane, two general anesthetics, produce unconsciousness through different neural mechanisms in mice. Ketamine activates many brain regions, especially cortical and subcortical areas involved in sensory, motor, emotional, and reward processing, with the temporal association areas acting as a strong hub, suggesting a top-down effect on consciousness by targeting higher-order cortical networks. Isoflurane primarily affects hypothalamic regions controlling neuroendocrine, autonomic, and homeostatic functions, with the locus coeruleus as a connector hub, indicating a bottom-up mechanism. Both anesthetics activate shared pathways for sensory processing, memory, cognition, reward, and autonomic control, revealing overlapping effects.
Cell reports
January 28, 2025
Yue Hu, Yifan Feng, Huoqing Luo et al.
6 citations
In mice, doses of ketamine that cause dissociation inhibit parvalbumin interneurons (PV-INs) in the retrosplenial cortex (RSC), increasing delta oscillations (1-3 Hz) and delta-gamma phase-amplitude coupling (δ-γ PAC) and producing dissociation-like behaviors. Directly inhibiting these neurons without ketamine also triggers delta oscillations, δ-γ PAC, and some dissociation-like behaviors. Activating RSC PV-INs or knocking down the NMDA receptor subunit NR1 and the HCN1 channel in these neurons reduces ketamine-induced delta oscillations, δ-γ PAC, and certain dissociation-like behaviors. The findings identify NR1 and HCN1 as ketamine targets in PV-INs that may cooperatively affect dissociation, suggesting potential therapeutic targets for dissociative symptoms.
National Science Review
September 5, 2025
Huoqing Luo, Ming Chen, Yingjie Ning et al.
1 citation
Ketamine produces rapid antidepressant effects by both blocking NMDA receptors and increasing serotonin levels through inhibition of the serotonin transporter (SERT). A cryogenic electron microscopy structure shows ketamine binding to SERT's central site. The elevated serotonin activates vasoactive intestinal peptide (VIP)-expressing interneurons, a cell type essential for ketamine's rapid effects. Inhibiting these neurons blocks the antidepressant actions, identifying a specific neural pathway. This dual mechanism offers potential strategies for developing rapidly acting antidepressants.
bioRxiv Preprint Server
June 3, 2023
Yue Hu, Wenjie Du, Jiangtao Qi et al.
1 citation
preprint
Ketamine and isoflurane, two common general anesthetics, produce unconsciousness through different brain mechanisms. Ketamine activates many cortical and subcortical regions involved in sensory, motor, emotional, and reward processing, with the temporal association areas acting as a strong hub, suggesting a top-down mechanism affecting consciousness by targeting higher-order cortical networks. Isoflurane predominantly influences hypothalamic regions controlling neuroendocrine, autonomic, and homeostatic functions, with the locus coeruleus as a connector hub, indicating a bottom-up mechanism. Both anesthetics also share effects on sensory, memory, reward, and autonomic pathways.