Role of Dorsomedial Hypothalamus GABAergic Neurons in Sleep–Wake States in Response to Changes in Ambient Temperature in Mice

Abstract

Good sleep quality is essential for maintaining the body’s attention during wakefulness, which is easily affected by external factors such as an ambient temperature. However, the mechanism by which an ambient temperature influences sleep–wake behaviors remains unclear. The dorsomedial hypothalamus (DMH) has been reported to be involved in thermoregulation. It also receives projection from the preoptic area, which is an important region for sleep and energy homeostasis and the suprachiasmatic nucleus—a main control area of the clock rhythm. Therefore, we hypothesized that the DMH plays an important role in the regulation of sleep related to ambient temperatures. In this study, we found that cold exposure (24/20/16/12 °C) increased wakefulness and decreased non–rapid eye movement (NREM) sleep, while warm exposure (32/36/40/44 °C) increased NREM sleep and decreased wakefulness compared to 28 °C conditions in wild-type mice. Then, using non-specific and specific apoptosis, we found that lesions of whole DMH neurons and DMH γ–aminobutyric acid (GABA)-ergic neurons induced by caspase-3 virus aggravated the fluctuation of core body temperature after warm exposure and attenuated the change in sleep–wake behaviors during cold and warm exposure. However, chemogenetic activation or inhibition of DMH GABAergic neurons did not affect the sleep–wake cycle. Collectively, our findings reveal an essential role of DMH GABAergic neurons in the regulation of sleep–wake behaviors elicited by a change in ambient temperature.

Glutamatergic neurons in the lateral periaqueductal gray mediate wakefulness and REM sleep through different pathways

“…EEG/EMG electrode implantation surgery. EEG recordings and analysis were performed as previously described 54,55,56 . Under pentobarbital sodium anesthesia (50 mg/kg, i.p.…”

Inputs and Outputs of the Mammalian Circadian Clock

“…Like most hypothalamic nuclei, the DMH comprises a heterogeneous population of neurons, but the subpopulation(s) of DMH neurons that regulate locomotor activity rhythms are not fully understood. Locomotor activity rhythms are unaffected by chemogenetically activating or genetically ablating GABAergic DMH neurons but are abolished when leptin receptor-expressing DMH neurons are genetically silenced [ 162 , 163 ]. Activating mWake -, brain-derived neurotrophic factor (BDNF)-, or prodynorphin-expressing DMH neurons each acutely increases locomotor activity.…”

Neurotransmitters in Type 2 Diabetes and the Control of Systemic and Central Energy Balance

“…Disruption of GABAergic neurons in the LHA dysregulates sleep and induces vigorous eating habits. A study looked at GABAergic neurons in the DMN region of the mouse hypothalamus and found that these neurons play a role in sleep–wake changes elicited by exposure to warmth in mice, indicative of their role in maintaining sleep and energy homeostasis [ 221 ].…”