ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Leptin acts via lateral hypothalamic area neurotensin neurons to inhibit orexin neurons by multiple GABA-independent mechanisms.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 120 citations in OpenAlex.
- The Neural Network of Orexin-A: Implications in Feeding Regulation and Obesity-Anxiety Comorbidity.Brain sciences · 2026Review
- Article
- A lateral hypothalamic neuronal population expressing leptin receptors counteracts anxiety to enable adaptive behavioral responses.Nature neuroscience · 2025Article
- Caloric Restriction, the Menstrual Cycle, and Sleep in Women Without Obesity.The Journal of clinical endocrinology and metabolism · 2025Article
- Review
- Molecular mechanisms and neural mediators of leptin action.Genes & development · 2025Review
- Lateral hypothalamus and eating: cell types, molecular identity, anatomy, temporal dynamics and functional roles.Experimental & molecular medicine · 2025Review
- Genetic and functional analyses of CTBP2 in anorexia nervosa and body weight regulation.Molecular psychiatry · 2025Article
- Leptin and Associated Neural Pathways Underlying Obesity-Induced Hypertension.Comprehensive Physiology · 2025Review
- Regulation of wakefulness by neurotensin neurons in the lateral hypothalamus.Experimental neurology · 2025Article
- Association of body-mass index with physiological brain pulsations across adulthood - a fast fMRI study.International journal of obesity (2005) · 2024Article
- Tryptophan metabolic pathway plays a key role in the stress-induced emotional eating.Current research in food science · 2024Article
- Orexin and MCH neurons: regulators of sleep and metabolism.Frontiers in neuroscience · 2023Review
- Leptin signaling and leptin resistance.Medical review (2021) · 2022Review
- Lateral hypothalamic galanin neurons are activated by stress and blunt anxiety-like behavior in mice.Behavioural brain research · 2022Article
- The physiological control of eating: signals, neurons, and networks.Physiological reviews · 2022 · on this mapArticle
- The Sleep-Promoting Ventrolateral Preoptic Nucleus: What Have We Learned over the Past 25 Years?International journal of molecular sciences · 2022Review
- A Neural Circuit Mechanism Controlling Breathing by Leptin in the Nucleus Tractus Solitarii.Neuroscience bulletin · 2022Article
- Multifaceted actions of melanin-concentrating hormone on mammalian energy homeostasis.Nature reviews. Endocrinology · 2021Review
- Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 4 institutions in 3 countries.
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Abstract
The adipocyte-derived hormone leptin modulates neural systems appropriately for the status of body energy stores. Leptin inhibits lateral hypothalamic area (LHA) orexin (OX; also known as hypocretin)-producing neurons, which control feeding, activity, and energy expenditure, among other parameters. Our previous results suggest that GABAergic LHA leptin receptor (LepRb)-containing and neurotensin (Nts)-containing (LepRb(Nts)) neurons lie in close apposition with OX neurons and control Ox mRNA expression. Here, we show that, similar to leptin, activation of LHA Nts neurons by the excitatory hM3Dq DREADD (designer receptor exclusively activated by designer drugs) hyperpolarizes membrane potential and suppresses action potential firing in OX neurons in mouse hypothalamic slices. Furthermore, ablation of LepRb from Nts neurons abrogated the leptin-mediated inhibition, demonstrating that LepRb(Nts) neurons mediate the inhibition of OX neurons by leptin. Leptin did not significantly enhance GABAA-mediated inhibitory synaptic transmission, and GABA receptor antagonists did not block leptin-mediated inhibition of OX neuron activity. Rather, leptin diminished the frequency of spontaneous EPSCs onto OX neurons. Furthermore, leptin indirectly activated an ATP-sensitive potassium (K(ATP)) channel in OX neurons, which was required for the hyperpolarization of OX neurons by leptin. Although Nts did not alter OX activity, galanin, which is coexpressed in LepRb(Nts) neurons, inhibited OX neurons, whereas the galanin receptor antagonist M40 (galanin-(1-12)-Pro3-(Ala-Leu)2-Ala amide) prevented the leptin-induced hyperpolarization of OX cells. These findings demonstrate that leptin indirectly inhibits OX neurons by acting on LHA LepRb(Nts) neurons to mediate two distinct GABA-independent mechanisms of inhibition: the presynaptic inhibition of excitatory neurotransmission and the opening of K(ATP) channels.
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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.