ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
GABAergic inhibition of histaminergic neurons regulates active waking but not the sleep-wake switch or propofol-induced loss of consciousness.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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60 citing papers in PubMed, 106 citations in OpenAlex.
- Subthalamic CaMKIIα-expressing neurons facilitate recovery from propofol anesthesia via the STN-ventral pallidum pathway.Cell biology and toxicology · 2026Article
- Immunoreactivity and distribution of Fos in the mouse brain following diverse general anesthetics.Scientific reports · 2025Article
- Comparative analysis of adenosine 1 receptor expression and function in hippocampal and hypothalamic neurons.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Loss-of-consciousness: sources of GABAergic input to the mesopontine tegmental anesthesia area.Frontiers in neuroscience · 2025Article
- Top-down modulation of the retinal code via histaminergic neurons of the hypothalamus.Science advances · 2024Article
- Homeostatic regulation of rapid eye movement sleep by the preoptic area of the hypothalamus.eLife · 2024Article
- Chemogenetic activation of histamine neurons promotes retrieval of apparently lost memories.Molecular brain · 2024Article
- Synapse-Specific Trapping of SNARE Machinery Proteins in the AnesthetizedThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Time to Wake Up! The Ongoing Search for General Anesthetic Reversal Agents.Anesthesiology · 2024Article
- Homeostatic regulation of REM sleep by the preoptic area of the hypothalamus.bioRxiv : the preprint server for biology · 2024Article
- The Diverse Network of Brain Histamine in Feeding: Dissect its Functions in a Circuit-Specific Way.Current neuropharmacology · 2024Review
- Microbial-Dependent Recruitment of Immature Myeloid Cells Promotes Intestinal Regeneration.Cellular and molecular gastroenterology and hepatology · 2024Article
- Neuro-orchestration of sleep and wakefulness.Nature neuroscience · 2023Review
- Histamine Release in the Prefrontal Cortex Excites Fast-Spiking Interneurons while GABA Released from the Same Axons Inhibits Pyramidal Cells.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The activation of GABAergic neurons in the hypothalamic tuberomammillary nucleus attenuates sevoflurane and propofol-induced anesthesia in mice.Frontiers in pharmacology · 2023Article
- Cre driver mouse lines for thalamocortical circuit mapping.The Journal of comparative neurology · 2022Article
- The Role of the Central Histaminergic System in Behavioral State Control.Current topics in behavioral neurosciences · 2022Review
- The Histamine System in Zebrafish Brain: Organization, Receptors, and Behavioral Roles.Current topics in behavioral neurosciences · 2022Article
- Chemogenetic modulation of histaminergic neurons in the tuberomamillary nucleus alters territorial aggression and wakefulness.Scientific reports · 2021Article
- Histamine, Neuroinflammation and Neurodevelopment: A Review.Frontiers in neuroscience · 2021Review
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Authors and funding
11 authors at 4 institutions in 2 countries.
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Abstract
The activity of histaminergic neurons in the tuberomammillary nucleus (TMN) of the hypothalamus correlates with an animal's behavioral state and maintains arousal. We examined how GABAergic inputs onto histaminergic neurons regulate this behavior. A prominent hypothesis, the "flip-flop" model, predicts that increased and sustained GABAergic drive onto these cells promotes sleep. Similarly, because of the histaminergic neurons' key hub-like place in the arousal circuitry, it has also been suggested that anesthetics such as propofol induce loss of consciousness by acting primarily at histaminergic neurons. We tested both these hypotheses in mice by genetically removing ionotropic GABA(A) or metabotropic GABA(B) receptors from histidine decarboxylase-expressing neurons. At the cellular level, histaminergic neurons deficient in synaptic GABA(A) receptors were significantly more excitable and were insensitive to the anesthetic propofol. At the behavioral level, EEG profiles were recorded in nontethered mice over 24 h. Surprisingly, GABAergic transmission onto histaminergic neurons had no effect in regulating the natural sleep-wake cycle and, in the case of GABA(A) receptors, for propofol-induced loss of righting reflex. The latter finding makes it unlikely that the histaminergic TMN has a central role in anesthesia. GABA(B) receptors on histaminergic neurons were dispensable for all behaviors examined. Synaptic inhibition of histaminergic cells by GABA(A) receptors, however, was essential for habituation to a novel environment.
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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.