ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2015
Optogenetic evidence for inhibitory signaling from orexin to MCH neurons via local microcircuits.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 122 citations in OpenAlex.
- Hypothalamic control of arousal.Reviews in endocrine & metabolic disorders · 2026Review
- Melanin-Concentrating Hormone (MCH): Role in Mediating Reward-Motivated and Emotional Behavior and the Behavioral Disturbances Produced by Repeated Exposure to Reward Substances.International journal of molecular sciences · 2025Review
- Review
- The role of orexin and MCH neurons in the hypothalamus in sleep-wake regulation and learning-forgetting balance.Frontiers in neuroscience · 2025Review
- Metabolic underpinnings of cancer-related fatigue.American journal of physiology. Endocrinology and metabolism · 2024Review
- Hypothalamic MCH Neurons: From Feeding to Cognitive Control.Function (Oxford, England) · 2024Review
- Mild Traumatic Brain Injury Affects Orexin/Hypocretin Physiology Differently in Male and Female Mice.Journal of neurotrauma · 2023Article
- Control of energy homeostasis by the lateral hypothalamic area.Trends in neurosciences · 2023Review
- Modulation of deep neural circuits with sonogenetics.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective.Endocrine reviews · 2022Review
- Whole-Brain Monosynaptic Afferents to Rostromedial Tegmental Nucleus Gamma-Aminobutyric Acid-Releasing Neurons in Mice.Frontiers in neuroscience · 2022Article
- The melanin-concentrating hormone system as a target for the treatment of sleep disorders.Frontiers in neuroscience · 2022Review
- Tau-driven degeneration of sleep- and wake-regulating neurons in Alzheimer's disease.Sleep medicine reviews · 2021Review
- Multifaceted actions of melanin-concentrating hormone on mammalian energy homeostasis.Nature reviews. Endocrinology · 2021Review
- Neurokinin B-Expressing Neurons of the Central Extended Amygdala Mediate Inhibitory Synaptic Input onto Melanin-Concentrating Hormone Neuron Subpopulations.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Melanin-concentrating hormone and food intake control: Sites of action, peptide interactions, and appetition.Peptides · 2021Review
- Energy state alters regulation of proopiomelanocortin neurons by glutamatergic ventromedial hypothalamus neurons: pre- and postsynaptic mechanisms.Journal of neurophysiology · 2021Article
- The dynamic regulation of appetitive behavior through lateral hypothalamic orexin and melanin concentrating hormone expressing cells.Physiology & behavior · 2021Review
- Altered sleep intensity upon DBS to hypothalamic sleep-wake centers in rats.Translational neuroscience · 2021Article
- Orexin/Hypocretin and MCH Neurons: Cognitive and Motor Roles Beyond Arousal.Frontiers in neuroscience · 2021Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
The lateral hypothalamus (LH) is a key regulator of multiple vital behaviors. The firing of brain-wide-projecting LH neurons releases neuropeptides promoting wakefulness (orexin/hypocretin; OH), or sleep (melanin-concentrating hormone; MCH). OH neurons, which coexpress glutamate and dynorphin, have been proposed to excite their neighbors, including MCH neurons, suggesting that LH may sometimes coengage its antagonistic outputs. However, it remains unclear if, when, and how OH actions promote temporal separation of the sleep and wake signals, a process that fails in narcolepsy caused by OH loss. To explore this directly, we paired optogenetic stimulation of OH cells (at rates that promoted awakening in vivo) with electrical monitoring of MCH cells in mouse brain slices. Membrane potential recordings showed that OH cell firing inhibited action potential firing in most MCH neurons, an effect that required GABAA but not dynorphin receptors. Membrane current analysis showed that OH cell firing increased the frequency of fast GABAergic currents in MCH cells, an effect blocked by antagonists of OH but not dynorphin or glutamate receptors, and mimicked by bath-applied OH peptide. In turn, neural network imaging with a calcium indicator genetically targeted to MCH neurons showed that excitation by bath-applied OH peptides occurs in a minority of MCH cells. Collectively, our data provide functional microcircuit evidence that intra-LH feedforward loops may facilitate appropriate switching between sleep and wake signals, potentially preventing sleep disorders.
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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.