Fast neurotransmitter identity of MCH neurons: Do contents depend on context?

• Published in: Frontiers in neuroendocrinology Vol. 70; p. 101069
• Main Authors: Beekly, B.G., Rupp, A., Burgess, C.R., Elias, C.F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-07-2023
• Subjects: GABA; gamma-Aminobutyric Acid; Glutamate; Glutamic Acid - pharmacology; Glutamic Acid - physiology; Hypothalamic Hormones - metabolism; Hypothalamic Hormones - pharmacology; Hypothalamus - metabolism; Melanin-concentrating hormone; Melanins - pharmacology; Melanins - physiology; Neurodevelopment; Neurons - metabolism; Neurotransmitter Agents; Neurotransmitter switching; Pituitary Hormones - pharmacology; Pituitary Hormones - physiology; Sex variables; GABA; Neurodevelopment; Neurotransmitter switching; Glutamate; Melanin-concentrating hormone; Sex variables
• ISSN: 0091-3022; 1095-6808; 1095-6808
• DOI: 10.1016/j.yfrne.2023.101069

•Neurotransmitter switching is increasingly recognized as a form of neuroplasticity.•Factors like age, sex, and environment may shape neurotransmitter identity.•The neurotransmitter identity of MCH neurons is still a matter of debate.•Inconsistent experimental design and animal models may explain the discrepant data.
Hypothalamic melanin-concentrating hormone (MCH) neurons participate in many fundamental neuroendocrine processes. While some of their effects can be attributed to MCH itself, others appear to depend on co-released neurotransmitters. Historically, the subject of fast neurotransmitter co-release from MCH neurons has been contentious, with data to support MCH neurons releasing GABA, glutamate, both, and neither. Rather than assuming a position in that debate, this review considers the evidence for all sides and presents an alternative explanation: neurochemical identity, including classical neurotransmitter content, is subject to change. With an emphasis on the variability of experimental details, we posit that MCH neurons may release GABA and/or glutamate at different points according to environmental and contextual factors. Through the lens of the MCH system, we offer evidence that the field of neuroendocrinology would benefit from a more nuanced and dynamic interpretation of neurotransmitter identity.