ArticleMolecular metabolism2015
Cholinergic neurons in the dorsomedial hypothalamus regulate mouse brown adipose tissue metabolism.
Article in Molecular metabolism, 2015. 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, 57 citations in OpenAlex.
- Thermoregulatory Dysfunction in Parkinson's Disease: Mechanisms, Implications, and Therapeutic Perspectives.Cells · 2025Review
- Immunohistochemical Profile of a Conspicuously Organized Structure in the Dorsal Forebrain of the Peacock Gudgeon, Tateurndina ocellicauda.The Journal of comparative neurology · 2025Article
- Developmental expression of α- and β- synuclein in the mouse retina.Brain structure & function · 2025Article
- Hypothalamic neural circuits regulating energy expenditure.Vitamins and hormones · 2025Review
- Interplay between the brain and adipose tissue: a metabolic conversation.EMBO reports · 2024Review
- The development of hepatic steatosis depends on the presence of liver-innervating parasympathetic cholinergic neurons in mice fed a high-fat diet.PLoS biology · 2024Article
- A parabrachial-hypothalamic parallel circuit governs cold defense in mice.Nature communications · 2023Article
- Article
- Neurons in the Dorsomedial Hypothalamus Promote, Prolong, and Deepen Torpor in the Mouse.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Autonomic control of energy balance and glucose homeostasis.Experimental & molecular medicine · 2022Review
- Central Neural Circuits Orchestrating Thermogenesis, Sleep-Wakefulness States and General Anesthesia States.Current neuropharmacology · 2022Review
- A hypothalamomedullary network for physiological responses to environmental stresses.Nature reviews. Neuroscience · 2022Review
- LETMD1 is required for mitochondrial structure and thermogenic function of brown adipocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Autonomic and cholinergic mechanisms mediating cardiovascular and temperature effects of donepezil in conscious mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Turn it off and on again: characteristics and control of torpor.Wellcome open research · 2021Review
- Optogenetic stimulation of the liver-projecting melanocortinergic pathway promotes hepatic glucose production.Nature communications · 2020Article
- Activation of the ARCFrontiers in neural circuits · 2020Article
- Neural control of fasting-induced torpor in mice.Scientific reports · 2019Article
- Brs3 neurons in the mouse dorsomedial hypothalamus regulate body temperature, energy expenditure, and heart rate, but not food intake.Nature neuroscience · 2018Article
- Is Adenosine Action Common Ground for NREM Sleep, Torpor, and Other Hypometabolic States?Physiology (Bethesda, Md.) · 2018Review
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveBrown adipose tissue (BAT) thermogenesis is critical in maintaining body temperature. The dorsomedial hypothalamus (DMH) integrates cutaneous thermosensory signals and regulates adaptive thermogenesis. Here, we study the function and synaptic connectivity of input from DMH cholinergic neurons to sympathetic premotor neurons in the raphe pallidus (Rpa).
methodsIn order to selectively manipulate DMH cholinergic neuron activity, we generated transgenic mice expressing channelrhodopsin fused to yellow fluorescent protein (YFP) in cholinergic neurons (choline acetyltransferase (ChAT)-Cre::ChR2-YFP) with the Cre-LoxP technique. In addition, we used an adeno-associated virus carrying the Cre recombinase gene to delete the floxed Chat gene in the DMH. Physiological studies in response to optogenetic stimulation of DMH cholinergic neurons were combined with gene expression and immunocytochemical analyses.
resultsA subset of DMH neurons are ChAT-immunopositive neurons. The activity of these neurons is elevated by warm ambient temperature. A phenotype-specific neuronal tracing shows that DMH cholinergic neurons directly project to serotonergic neurons in the Rpa. Optical stimulation of DMH cholinergic neurons decreases BAT activity, which is associated with reduced body core temperature. Furthermore, elevated DMH cholinergic neuron activity decreases the expression of BAT uncoupling protein 1 (Ucp1) and peroxisome proliferator-activated receptor γ coactivator 1 α (Pgc1α) mRNAs, markers of BAT activity. Injection of M2-selective muscarinic receptor antagonists into the 4th ventricle abolishes the effect of optical stimulation. Single cell qRT-PCR analysis of retrogradely identified BAT-projecting neurons in the Rpa shows that all M2 receptor-expressing neurons contain tryptophan hydroxylase 2. In animals lacking the Chat gene in the DMH, exposure to warm temperature reduces neither BAT Ucp1 nor Pgc1α mRNA expression.
conclusionDMH cholinergic neurons directly send efferent signals to sympathetic premotor neurons in the Rpa. Elevated cholinergic input to this area reduces BAT activity through activation of M2 mAChRs on serotonergic neurons. Therefore, the direct DMH(ACh)-Rpa(5-HT) pathway may mediate physiological heat-defense responses to elevated environmental temperature.
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