Neurons containing melanin-concentrating hormone (MCH) in the posterior lateral hypothalamus play an integral role in rapid eye movement sleep (REMs) regulation. As MCH neurons also contain a variety of other neuropeptides [e.g., cocaine- and amphetamine-regulated transcript (CART) and nesfatin-1] and neurotransmitters (e.g., glutamate), the specific neurotransmitter responsible for REMs regulation is not known. We hypothesized that glutamate, the primary fast-acting neurotransmitter in MCH neurons, is necessary for REMs regulation. To test this hypothesis, we deleted vesicular glutamate transporter (Vglut2; necessary for synaptic release of glutamate) specifically from MCH neurons by crossing MCH-Cre mice (expressing Cre recombinase in MCH neurons) with Vglut2flox/flox mice (expressing LoxP-modified alleles of Vglut2), and studied the amounts, architecture and diurnal variation of sleep-wake states during baseline conditions. We then activated the MCH neurons lacking glutamate neurotransmission using chemogenetic methods and tested whether these MCH neurons still promoted REMs. Our results indicate that glutamate in MCH neurons contributes to normal diurnal variability of REMs by regulating the levels of REMs during the dark period, but MCH neurons can promote REMs even in the absence of glutamate.

Body temperature, Chemogenetics, Conditional knockout, Diurnal rhythms, Lateral hypothalamus, Locomotor activity, Paradoxical sleep
Brain Structure and Function
Department of Neuroscience

Naganuma, F. (Fumito), Bandaru, S.S. (Sathyajit S.), Absi, G. (Gianna), Chee, M, & Vetrivelan, R. (Ramalingam). (2018). Melanin-concentrating hormone neurons promote rapid eye movement sleep independent of glutamate release. Brain Structure and Function. doi:10.1007/s00429-018-1766-2