Melanin-concentrating hormone neurons promote rapid eye movement sleep independent of glutamate release

• Published in: Brain Structure and Function 2019-01, Vol.224 (1), p.99-110
• Main Authors: Naganuma, Fumito, Bandaru, Sathyajit S., Absi, Gianna, Chee, Melissa J., Vetrivelan, Ramalingam
• Format: Article
• Language: English
• Subjects: Amphetamines; Animals; Biomedical and Life Sciences; Biomedicine; Cell Biology; Circadian Rhythm; Cocaine; Cocaine- and amphetamine-regulated transcript protein; Cre recombinase; Diurnal; Eye movements; Glutamic Acid - metabolism; Glutamic acid transporter; Hypothalamic Hormones - genetics; Hypothalamic Hormones - metabolism; Hypothalamus (lateral); Hypothalamus, Posterior - cytology; Hypothalamus, Posterior - metabolism; Male; Melanin; Melanin-concentrating hormone; Melanins - genetics; Melanins - metabolism; Mice, Transgenic; Neurology; Neurons; Neurons - metabolism; Neuropeptides; Neurosciences; Neurotransmission; Neurotransmitters; Original Article; Photoperiod; Pituitary Hormones - genetics; Pituitary Hormones - metabolism; REM sleep; Rodents; Sleep; Sleep and wakefulness; Sleep, REM; Time Factors; Transcription; Vesicular Glutamate Transport Protein 2 - genetics; Vesicular Glutamate Transport Protein 2 - metabolism; Wakefulness
• ISSN: 1863-2653; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-018-1766-2

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 Vglut2 flox/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.