0104 TEMPORALLY CONTROLLED CELL-SPECIFIC ABLATION OF MELANIN-CONCENTRATING HORMONE (MCH) NEURONS ATTENUATE NON-REM SLEEP IN MICE

Abstract

Melanin-concentrating hormone (MCH) is a neuropeptide produced in neurons sparsely distributed in the lateral hypothalamic area. Recent studies have reported that MCH neurons are active during rapid eye movement (REM) sleep, but their physiological role in the regulation of sleep/wakefulness is not fully understood. To determine the physiological role of MCH neurons, we assessed sleep in MCH-tetracycline-controlled transactivator (tTA); tetracycline operator (TetO)-diphtheria toxin A (DTA) transgenic (TG) mice that enables temporal control of MCH neuronal ablation by cell-specific expression of DTA. TG mice were fed with chow containing Dox (100 mg/kg) until 10 weeks of age. Then, Dox(+) chow was replaced with Dox(-) chow for another 4 weeks. Control mice received Dox(+) chow throughout the experimental period. These mice were chronically implanted with EEG and EMG electrodes for polysomnographic recording of sleep/wake states. The vigilance states were automatically classified by SleepSign ver.3 software. The number of MCH(+) neurons were assessed immunohistochemically. When 90% of the MCH neurons were ablated, NREM sleep amount was significantly reduced. On the other hand, no significant difference in REM sleep amount was observed. The EEG power spectra from both NREM and REM sleep of MCH neuronal ablated mice were indistinguishable from those of before ablation, suggesting that ablation of the MCH neurons does not affect the nature of basal cortical activity. Next, we assessed sleep profile in response to fasting in MCH neuron ablated mice. Their sleep response as well as the amount food intake during and after fasting (re-feeding) was mostly identical as control mice. From our result, the main role of MCH neurons in the regulation of sleep is thought be the maintenance of NREM sleep. In spite of many reports suggested the role of MCH in the fasting condition, there were no significant differences in sleep response in MCH neurons ablation mice. Thus, MCH neurons have a minor role to regulate sleep in response to fasting. This work was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (15K07140) and the Akiyama Life Science Foundation.