Melanin-Concentrating Hormone Neurons Release Glutamate for Feedforward Inhibition of the Lateral Septum
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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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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).”
From Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum (2025) · cites this paper as Chee et al., 2015
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Le contrôle moteur dans tous les états
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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
- Publisher
- Society for Neuroscience
- Published
- 2015-02-25
- Volume
- 35
- Issue
- 8
- Pages
- 3644-3651
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6605558
- 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
- hybrid
- doi.org
- Licence
- 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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