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

Lei Li,Yi-Qun Wang,Xiao Sun,Zhi-Li Huang,Meng-Qi Zhang,Wen-Ying Liu

doi:10.3390/ijms23031270

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.

Highlights

Sleep, core body temperature, and ambient temperature are tightly interconnected in homeothermic mammals [1]
To determine the reliability of the method and explore the cold and warm exposure temperature suitable for this research, we studied the effects of gradient temperature exposure on sleep–wake behavior in wild type (WT) mice
The results revealed that cold exposure significantly increased arousal time and reduced non-rapid eye movement (NREM) sleep and rapid eye movement (REM) sleep in dorsomedial hypothalamus (DMH)–WT–eGFP (n = 11, p < 0.05) and DMH–WT–Casp3 (n = 7, p < 0.05) mice during the first hour

Summary

Introduction

Core body temperature, and ambient temperature are tightly interconnected in homeothermic mammals [1]. How the temperature signal interacts with sleep–wake behaviors and which brain regions are involved in this interaction remains unclear. The dorsomedial hypothalamus (DMH) is a brain region adjacent to the third ventricle and located caudal and ventral to the paraventricular nucleus of the hypothalamus, which is critical for arousal promotion and maintenance [4], food intake, and locomotor activity [5]. The lateral portion of the DMH is adjacent to both the fornix and the lateral hypothalamic area [6], which is a heterogeneous nucleus [7] associated with sleep–wake regulation [8], feeding behavior, and energy metabolism [9]. The DMH receives projections from the center of body temperature regulation—the preoptic area (POA) [10] of the hypothalamus, and has bidirectional projections with the site of the principal circadian clock—the suprachiasmatic nucleus (SCN) [11–16]. We hypothesized that the DMH GABAergic neurons, which are most densely distributed in the DMH, are involved in body temperature regulation during sleep in mice

Methods

Results

Conclusion