Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia in mice.

Posterior subthalamic nucleus (PSTh) mediates innate fear-associated hypothermia in mice.
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DOI:
10.1038/s41467-021-22914-6
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发表时间:
2021-05-11
影响因子:
16.6
通讯作者:
Liu Q
Liu Q
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Liu C;Lee CY;Asher G;Cao L;Terakoshi Y;Cao P;Kobayakawa R;Kobayakawa K;Sakurai K;Liu Q

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与恐惧相关的体温调节的神经机制仍不清楚。天生的恐惧气味2-甲基-2-噻唑啉(2 MT)在野生型小鼠中引起快速体温降低和尾部温度升高,表明血管舒张诱导的散热,但在缺乏Trpa 1的小鼠中没有-2 MT的化学传感器。在这里,我们报告说,Trpa 1 −/−小鼠表现出减少2 MT诱发的c-fos表达在丘脑底后核(PSTh),外侧臂旁亚核(PBel)和孤束核(NTS)。尽管破伤风毒素轻链介导的NTS投射PSTh神经元的失活抑制,但直接PSTh-喙侧NTS通路的光遗传学激活诱导体温降低和尾部血管舒张。此外,通过捕获激活的神经元系综(CANE)选择性光刺激2 MT激活的PSTh投射的PBel神经元导致体温过低。相反,PBel或PSTh中vGlut 2+神经元或PSTh投射PBel神经元的化学发生抑制减弱2 MT诱发的低温和尾部血管舒张。这些研究确定PSTh作为一个主要的体温调节枢纽,连接PBel的NTS介导2 MT诱发的先天性恐惧相关的低温和尾部血管舒张。先天的和后天习得的恐惧可以引起哺乳动物体温的快速变化。作者认为丘脑底后核是一个主要的体温调节中枢,它连接臂旁外侧亚核和孤束核,以介导恐惧诱发的体温降低。
The neural mechanisms of fear-associated thermoregulation remain unclear. Innate fear odor 2-methyl-2-thiazoline (2MT) elicits rapid hypothermia and elevated tail temperature, indicative of vasodilation-induced heat dissipation, in wild-type mice, but not in mice lacking Trpa1–the chemosensor for 2MT. Here we report that Trpa1−/− mice show diminished 2MT-evoked c-fos expression in the posterior subthalamic nucleus (PSTh), external lateral parabrachial subnucleus (PBel) and nucleus of the solitary tract (NTS). Whereas tetanus toxin light chain-mediated inactivation of NTS-projecting PSTh neurons suppress, optogenetic activation of direct PSTh-rostral NTS pathway induces hypothermia and tail vasodilation. Furthermore, selective opto-stimulation of 2MT-activated, PSTh-projecting PBel neurons by capturing activated neuronal ensembles (CANE) causes hypothermia. Conversely, chemogenetic suppression of vGlut2+ neurons in PBel or PSTh, or PSTh-projecting PBel neurons attenuates 2MT-evoked hypothermia and tail vasodilation. These studies identify PSTh as a major thermoregulatory hub that connects PBel to NTS to mediate 2MT-evoked innate fear-associated hypothermia and tail vasodilation. Innate and learned fear can induce rapid changes in body temperature of mammals. The authors identify the posterior subthalamic nucleus as a major thermoregulatory hub that connects the external lateral parabrachial subnucleus to the nucleus of the solitary tract to mediate fear-evoked hypothermia.
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