Department of Integrative Physiology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Japan.
Nagoya University Institute for Advanced Research, Nagoya, 464-8601, Japan.
J Neurosci. 2023 Jul 12;43(28):5221-5240. doi: 10.1523/JNEUROSCI.0643-23.2023. Epub 2023 Jun 20.
Thermoregulatory behavior in homeothermic animals is an innate behavior to defend body core temperature from environmental thermal challenges in coordination with autonomous thermoregulatory responses. In contrast to the progress in understanding the central mechanisms of autonomous thermoregulation, those of behavioral thermoregulation remain poorly understood. We have previously shown that the lateral parabrachial nucleus (LPB) mediates cutaneous thermosensory afferent signaling for thermoregulation. To understand the thermosensory neural network for behavioral thermoregulation, in the present study, we investigated the roles of ascending thermosensory pathways from the LPB in avoidance behavior from innocuous heat and cold in male rats. Neuronal tracing revealed two segregated groups of LPB neurons projecting to the median preoptic nucleus (MnPO), a thermoregulatory center (LPB→MnPO neurons), and those projecting to the central amygdaloid nucleus (CeA), a limbic emotion center (LPB→CeA neurons). While LPB→MnPO neurons include separate subgroups activated by heat or cold exposure of rats, LPB→CeA neurons were only activated by cold exposure. By selectively inhibiting LPB→MnPO or LPB→CeA neurons using tetanus toxin light chain or chemogenetic or optogenetic techniques, we found that LPB→MnPO transmission mediates heat avoidance, whereas LPB→CeA transmission contributes to cold avoidance. electrophysiological experiments showed that skin cooling-evoked thermogenesis in brown adipose tissue requires not only LPB→MnPO neurons but also LPB→CeA neurons, providing a novel insight into the central mechanism of autonomous thermoregulation. Our findings reveal an important framework of central thermosensory afferent pathways to coordinate behavioral and autonomous thermoregulation and to generate the emotions of thermal comfort and discomfort that drive thermoregulatory behavior. Coordination of behavioral and autonomous thermoregulation is important for maintaining thermal homeostasis in homeothermic animals. However, the central mechanism of thermoregulatory behaviors remains poorly understood. We have previously shown that the lateral parabrachial nucleus (LPB) mediates ascending thermosensory signaling that drives thermoregulatory behavior. In this study, we found that one pathway from the LPB to the median preoptic nucleus mediates heat avoidance, whereas the other pathway from the LPB to the central amygdaloid nucleus is required for cold avoidance. Surprisingly, both pathways are required for skin cooling-evoked thermogenesis in brown adipose tissue, an autonomous thermoregulatory response. This study provides a central thermosensory network that coordinates behavioral and autonomous thermoregulation and generates thermal comfort and discomfort that drive thermoregulatory behavior.
恒温动物的体温调节行为是一种内在行为,旨在协调自主体温调节反应,防止身体核心温度受到环境热挑战。与自主体温调节的中心机制的研究进展相比,行为体温调节的中心机制仍知之甚少。我们之前已经表明,外侧臂旁核 (LPB) 介导了皮肤温度感觉传入信号,以进行体温调节。为了了解行为体温调节的温度感觉神经网络,在本研究中,我们调查了来自 LPB 的上升温度感觉途径在雄性大鼠避免无害热和冷的行为中的作用。神经元追踪显示,LPB 投射到调节中心(LPB→MnPO 神经元)和投射到杏仁中央核(CeA,边缘情绪中心)的两组分离的 LPB 神经元(LPB→CeA 神经元)。虽然 LPB→MnPO 神经元包括因大鼠暴露于热或冷而被激活的单独亚群,但 LPB→CeA 神经元仅因冷暴露而被激活。通过使用破伤风毒素轻链或化学遗传或光遗传技术选择性地抑制 LPB→MnPO 或 LPB→CeA 神经元,我们发现 LPB→MnPO 传递介导了热回避,而 LPB→CeA 传递有助于冷回避。电生理实验表明,棕色脂肪组织的皮肤冷却引起的产热不仅需要 LPB→MnPO 神经元,还需要 LPB→CeA 神经元,为自主体温调节的中枢机制提供了新的见解。我们的发现揭示了中央温度感觉传入途径协调行为和自主体温调节并产生驱动体温调节行为的热舒适和不适情绪的重要框架。行为和自主体温调节的协调对于维持恒温动物的体温平衡很重要。然而,体温调节行为的中枢机制仍知之甚少。我们之前已经表明,外侧臂旁核 (LPB) 介导了驱动体温调节行为的上升温度感觉信号。在这项研究中,我们发现 LPB 到中脑视前核的一条途径介导了热回避,而 LPB 到杏仁中央核的另一条途径则是冷回避所必需的。令人惊讶的是,两条途径都需要皮肤冷却引起的棕色脂肪组织产热,这是一种自主体温调节反应。这项研究提供了一个中央温度感觉网络,该网络协调行为和自主体温调节,并产生热舒适和不适,从而驱动体温调节行为。
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