Cited by 112Regulation of Appetite and ObesityNeuroscience and Neuropharmacology ResearchSleep and Wakefulness Research

Melanin-Concentrating Hormone Neurons Release Glutamate for Feedforward Inhibition of the Lateral Septum

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Chee, Melissa J.S., Arrigoni, Elda, Maratos-Flier, Eleftheria·2015·The Journal of Neuroscience

Abstract

Melanin-concentrating hormone (MCH) regulates vital physiological functions, including energy balance and sleep. MCH cells are thought to be GABAergic, releasing GABA to inhibit downstream targets. However, there is little experimental support for this paradigm. To better understand the synaptic mechanisms of mouse MCH neurons, we performed neuroanatomical mapping and characterization followed by optogenetics to test their functional connectivity at downstream targets. Synaptophysin-mediated projection mapping showed that the lateral septal nucleus (LS) contained the densest accumulation of MCH nerve terminals. We then expressed channelrhodopsin-2 in MCH neurons and photostimulated MCH projections to determine their effect on LS activity. Photostimulation of MCH projections evoked a monosynaptic glutamate release in the LS. Interestingly, this led to a feedforward inhibition that depressed LS firing by a robust secondary GABA release. This study presents a circuit analysis between MCH and LS neurons and confirms their functional connection via monosynaptic and polysynaptic pathways. Our findings indicate that MCH neurons are not exclusively GABAergic and reveal a glutamate-mediated, feedforward mechanism that inhibits LS cells.

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Crossref · 10.1523/jneurosci.4187-14.2015

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  • Extracellular glutamate released in the LS likely derives from glutamatergic neurons projecting to the LS, including those located in the hippocampus and hypothalamus.

    “Extracellular glutamate released in the LS likely derives from glutamatergic neurons projecting to the LS, including those located in the hippocampus (Zaczek et al., 1979;Gallagher et al., 1995) and in the hypothalamus (Chee et al., 2015).”

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Authors
Chee, M. J. S., Arrigoni, E., & Maratos-Flier, E.
Affiliations
Beth Israel Deaconess Medical Center (US)
Venue
The Journal of Neuroscience
Published
2015-02-25
Volume
35
Issue
8
Pages
3644-3651
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W1970610262
Cited by
112
References
48
Citations by year
2026: 11 · 2025: 7 · 2024: 11 · 2023: 11 · 2022: 8 · 2021: 11 · 2020: 11 · 2019: 5 · 2018: 13 · 2017: 10 · 2016: 11 · 2015: 3
FWCI
6.84
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Keywords
melanin-concentrating hormone, lateral septal nucleus, glutamate release, feedforward inhibition, GABAergic neurons, MCH neurons, synaptic connectivity, monosynaptic pathway, polysynaptic pathways, optogenetic stimulation, channelrhodopsin-2, neural circuits
MeSH terms
Animals, Hypothalamic Hormones, Melanins, Pituitary Hormones, Septal Nuclei, Presynaptic Terminals, Glutamic Acid, Excitatory Postsynaptic Potentials, Feedback, Physiological, Mice, Inhibitory Postsynaptic Potentials, GABAergic Neurons, Optogenetics

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