0064 Lateral Hypothalamic Control of REM Sleep Expression During Ambient Temperature Warming

Abstract

Sleep and thermoregulation are tightly integrated. Moreover, ambient temperature (Ta) warming preferentially increases REM sleep over NREM sleep across species. Although the role of the anterior hypothalamus in thermoregulation and NREM sleep expression are well documented, the hypothalamic control of REM sleep during ambient temperature manipulation remains to be determined. We examined the role of the posterior lateral hypothalamus (LH) melanin concentrating hormone (MCH) system in the modulation of REM sleep during Ta manipulation. Genetically engineered MCH-R1-knockout (KO) mice or MCH::cre mice implanted with cortical EEG and neck EMG electrodes were used for these experiments. Mice were housed at 23.0 ± 1.0°C in their home cages in a temperature-controlled cabinet. During the light period at two hour intervals, four bouts of rapid Ta warming to a maximum of 31.7°C were achieved for 30 minutes with a thermostatically controlled combination of convection heater and indirect infrared lamp. To optogenetically stimulate MCH neurons, we stereotactically injected AAV2-ChR2-eYFP or AAV2-eYFP (controls) in the LH of MCH::Cre mice. In wild type (WT) controls, REM sleep was significantly increased in the warm (27.5–31°C) versus cool (24.0–27.5˚C) condition. However, MCH-R1-KO mice showed no significant changes in REM sleep as a function of Ta. Random semi-chronic optical activation of MCH neurons significantly increased NREM-to-REM sleep transitions, and prolonged REM sleep durations compared to YFP controls, but did not affect NREM sleep. Additional Ta warming had an additive effect on increasing REM sleep, demonstrating that optical stimulation of MCH neurons in combination with Ta warming was able to “over-drive” the expression of REM sleep beyond what optical stimulation or Ta warming alone could achieve. Indeed, optical stimulation had the same effect on increasing REM sleep expression as Ta warming in the YFP control mice. These data support a key role for the MCH system in the output expression of REM sleep during Ta manipulation, and show that concomitant MCH activation with Ta warming can over-express this effect. Ohio Sleep Medicine and Neuroscience Institute, Inselspital Bern University Hospital.