Hypothalamic melanin-concentrating hormone regulates hippocampus-dorsolateral septum activity

• Published in: Nature neuroscience Vol. 25; no. 1; pp. 61 - 71
• Main Authors: Liu, Jing-Jing, Tsien, Richard W., Pang, Zhiping P.
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.01.2022; Nature Publishing Group
• Subjects: 631/378/1697/2602; 631/378/340; 631/378/548/1964; Animal Genetics and Genomics; Animals; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Energy balance; Firing pattern; Hippocampus; Hippocampus - physiology; Homeostasis; Hypothalamic Hormones - metabolism; Hypothalamus; Melanin; Melanin-concentrating hormone; Melanins; Memory tasks; Mice; Neurobiology; Neurosciences; Physiological effects; Physiology; Pituitary Hormones; Polypeptides; Septum; Signaling; Spatial analysis; Spatial memory; γ-Aminobutyric acid
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-021-00984-5

Hypothalamic melanin-concentrating hormone (MCH) polypeptide contributes to regulating energy homeostasis, sleep and memory, although the mechanistic bases of its effects are unknown. In this study, in mice, we uncovered the physiological mechanism underlying the functional role of MCH signaling in projections to the dorsolateral septum (dLS), a region involved in routing hippocampal firing rhythms and encoding spatial memory based on such rhythms. Firing activity within the dLS in response to dorsal CA3 (dCA3) excitation is limited by strong feed-forward inhibition (FFI). We found that MCH synchronizes dLS neuronal firing with its dCA3 inputs by enhancing GABA release, which subsequently reduces the FFI and augments dCA3 excitatory input strength, both via pre-synaptic mechanisms. At the functional level, our data reveal a role for MCH signaling in the dLS in facilitating spatial memory. These findings support a model in which peptidergic signaling within the dLS modulates dorsal hippocampal output and supports memory encoding. The authors uncovered the physiological mechanism underlying the functional role of melanin-concentrating hormone in the dorsolateral septum, a region involved in routing hippocampal firing rhythms and encoding spatial memory.