Median preoptic glutamatergic neurons promote thermoregulatory heat loss and water consumption in mice

Median preoptic glutamatergic neurons promote thermoregulatory heat loss and water consumption in mice
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DOI:
10.1113/jp274667
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发表时间:
2017-10-15
影响因子:
5.5
通讯作者:
Saper, Clifford B.
Saper, Clifford B.
中科院分区:
医学1区
文献类型:
--
作者:
Abbott, Stephen B. G.;Saper, Clifford B.

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中位视前核(MnPO)在水/电解质平衡和体温调节的整合中起着重要作用,但我们对这些功能在细胞水平上的理解有限。利用Cre-Lox基因靶向VGluT2转基因小鼠的Channelrhodospin 2,我们在监测小鼠饮水行为和核心温度的同时,研究了谷氨酸能MnPO神经元刺激对自由行为小鼠的影响。刺激在62%(13/21)小鼠中产生强烈的低温反应(核心温度:-4.6 +/- 0.5℃,与对照组相比P= 0.001),引起皮肤血管扩张。刺激谷氨酸能MnPO神经元也在82%(18/22)的小鼠中产生了强劲的饮酒行为。在20分钟的试验中,刺激期间饮水的小鼠在黑暗阶段消耗912 +/- 163 μ l (n = 8),但在光照阶段明显减少(421 +/- 83 μ l, P=0.0025)。此外,在刺激期间饮酒被抑制,因为水被摄入,提示前系统反馈门控饮酒。50%的小鼠在刺激过程中出现了体温过低和饮酒的情况。刺激部位的解剖图谱显示,与体温过低相关的部位比与饮酒相关的部位更靠近前腹侧,尽管有大量重叠。因此,单独但重叠的谷氨酸能MnPO神经元群的激活对饮酒和自主体温调节机制产生影响,为它们频繁协调(例如在高温期间)提供了结构基础。
The median preoptic nucleus (MnPO) serves an important role in the integration of water/electrolyte homeostasis and thermoregulation, but we have a limited understanding these functions at a cellular level. Using Cre-Lox genetic targeting of Channelrhodospin 2 in VGluT2 transgenic mice, we examined the effect of glutamatergic MnPO neuron stimulation in freely behaving mice while monitoring drinking behaviour and core temperature. Stimulation produced a strong hypothermic response in 62% (13/21) of mice (core temperature: -4.6 +/- 0.5 degrees C, P= 0.001 vs. controls) caused by cutaneous vasodilatation. Stimulating glutamatergic MnPO neurons also produced robust drinking behaviour in 82% (18/22) of mice. Mice that drank during stimulation consumed 912 +/- 163 mu l (n = 8) during a 20min trial in the dark phase, but markedly less during the light phase (421 +/- 83 mu l, P=0.0025). Also, drinking during stimulation was inhibited as water was ingested, suggesting pre-systemic feedback gating of drinking. Both hypothermia and drinking during stimulation occurred in 50% of mice tested. Anatomical mapping of the stimulation sites showed that sites associated with hypothermia were more anteroventral than those associated with drinking, although there was substantial overlap. Thus, activation of separate but overlapping populations of glutamatergic MnPO neurons produces effects on drinking and autonomic thermoregulatory mechanisms, providing a structural basis for their frequently being coordinated (e.g. during hyperthermia).