ArticleThe Journal of clinical investigation2017
Endocannabinoid signaling in hypothalamic circuits regulates arousal from general anesthesia in mice.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 49 citations in OpenAlex.
- Anesthetic State-Dependent Bidirectional Control of States of Consciousness via Heterogeneous Medial Septum to Ventral Tegmental Area Circuits under Sevoflurane in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Wakefulness regulation of memory encoding and retrieval: structure and activity.National science review · 2026Review
- Neural Circuit Mechanisms of General Anaesthesia Induction: Current Advances and Future Directions.Current neuropharmacology · 2026Review
- Endocannabinoids inhibit contextual fear memory generalization via hippocampal GABAergic synaptic transmission.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endocannabinoid interference blocks post-global cerebral ischemia depression through prefrontal cortico-amygdala projections.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- [Activation of astrocytes in the dorsomedial hypothalamus accelerates sevoflurane anesthesia emergence in mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Neural Network Mechanisms Underlying General Anesthesia: Cortical and Subcortical Nuclei.Neuroscience bulletin · 2024Review
- Laminar Distribution of Cannabinoid Receptor 1 in the Prefrontal Cortex of Nonhuman Primates.Molecular neurobiology · 2024Article
- Glutamatergic neurons of piriform cortex delay induction of inhalational general anesthesia.Fundamental research · 2024Article
- BNST GABAergic neurons modulate wakefulness over sleep and anesthesia.Communications biology · 2024Article
- Prelimbic cortical pyramidal neurons to ventral tegmental area projections promotes arousal from sevoflurane anesthesia.CNS neuroscience & therapeutics · 2024Article
- The PrLiScience · 2023Article
- Dexmedetomidine modulates neuronal activity of horizontal limbs of diagonal band via α2 adrenergic receptor in mice.BMC anesthesiology · 2023Article
- A role of prefrontal cortico-hypothalamic projections in wake promotion.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- GABAergic neurons in the dorsomedial hypothalamus regulate states of consciousness in sevoflurane anesthesia.iScience · 2023Article
- Divergent Neural Activity in the VLPO During Anesthesia and Sleep.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Claustrum modulates behavioral sensitivity and EEG activity of propofol anesthesia.CNS neuroscience & therapeutics · 2023Article
- Glutamatergic neurons in paraventricular nucleus of the thalamus regulate the recovery from isoflurane anesthesia.BMC anesthesiology · 2022Article
- Endocannabinoid signaling regulates post-operative delirium through glutamatergic mediodorsal thalamus-prelimbic prefrontal cortical projection.Frontiers in aging neuroscience · 2022Article
- Activation of astroglial CB1R mediates cerebral ischemic tolerance induced by electroacupuncture.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 4 countries.
Funding
Abstract
Consciousness can be defined by two major attributes: awareness of environment and self, and arousal, which reflects the level of awareness. The return of arousal after general anesthesia presents an experimental tool for probing the neural mechanisms that control consciousness. Here we have identified that systemic or intracerebral injection of the cannabinoid CB1 receptor (CB1R) antagonist AM281 into the dorsomedial nucleus of the hypothalamus (DMH) - but not the adjacent perifornical area (Pef) or the ventrolateral preoptic nucleus of the hypothalamus (VLPO) - accelerates arousal in mice recovering from general anesthesia. Anesthetics selectively activated endocannabinoid (eCB) signaling at DMH glutamatergic but not GABAergic synapses, leading to suppression of both glutamatergic DMH-Pef and GABAergic DMH-VLPO projections. Deletion of CB1R from widespread cerebral cortical or prefrontal cortical (PFC) glutamatergic neurons, including those innervating the DMH, mimicked the arousal-accelerating effects of AM281. In contrast, CB1R deletion from brain GABAergic neurons or hypothalamic glutamatergic neurons did not affect recovery time from anesthesia. Inactivation of PFC-DMH, DMH-VLPO, or DMH-Pef projections blocked AM281-accelerated arousal, whereas activation of these projections mimicked the effects of AM281. We propose that decreased eCB signaling at glutamatergic terminals of the PFC-DMH projection accelerates arousal from general anesthesia through enhancement of the excitatory DMH-Pef projection, the inhibitory DMH-VLPO projection, or both.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.