Prostaglandin E2-increased thermosensitivity of anterior hypothalamic neurons is associated with depressed inhibition.
Prostaglandin E2-increased thermosensitivity of anterior hypothalamic neurons is associated with depressed inhibition.
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DOI：
10.1073/pnas.0308718101
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发表时间：
2004-02
影响因子：
11.1
通讯作者：
I. Tabarean;M. Behrens;T. Bártfai;H. Korn
中科院分区：
文献类型：
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作者：
I. Tabarean;M. Behrens;T. Bártfai;H. Korn
下丘脑前部神经元的温度反应被认为是调节恒温动物温度设定值的关键因素。我们利用电生理和免疫细胞化学技术研究了小鼠AH神经元对加热的敏感性。在对照实验中，当温度从37℃升高到40℃时，3- 5周龄的细胞中只有约9%的细胞表现出基本放电率的变化。在细胞外培养基中添加内源性热原前列腺素E2 （PGE2）“引物”后，这一比例增加到27%。在这些神经元中，放电频率显著增加，γ -氨基丁酸（GABA）抑制突触后电位的频率显著降低。相比之下，所记录细胞的静息电位和膜电阻保持不变。研究发现，PGE2可降低表达e -前列腺素受体3型的gaba能神经元亚群中细胞外信号调节激酶1和2的磷酸化水平。U0126对ERK1/2的抑制作用与PGE2相似。这些数据表明，PGE2主要作用于gaba能突触前细胞的兴奋性，很可能是通过改变电压门控K+通道。我们的研究结果还表明，热敏程度远不是一类特殊神经元的固有特性，而是可以通过突触活动强烈调节的，并且是下丘脑神经元比以前认为的更具适应性的特性。
Temperature responses of anterior hypothalamic neurons are considered key elements in the regulation of the temperature setpoint of homeotherms. We have investigated the sensitivity to warming of cultured neurons of the AH from mice with electrophysiological and immunocytochemical techniques. In control experiments, only approximately 9% of the 3- to 5-week-old cells exhibited changes of their basic firing rate when the temperature was raised from 37 degrees C to 40 degrees C. This ratio was increased to 27% after the cultures were "primed" by adding prostaglandin E2 (PGE2), an endogenous pyrogen, in the extracellular medium. In these neurons the firing rate was significantly increased, and the frequency of the gamma gamma-aminobutyric acid (GABA) inhibitory postsynaptic potentials was markedly decreased. In contrast, the resting potential and membrane resistance of the recorded cells remained unchanged. PGE2 was found to decrease the level of phosphorylation of the extracellular signal-regulated kinases 1 and 2 in a subset of GABAergic neurons that express the E-prostanoid receptor type 3. Inhibition of ERK1/2 by U0126 mimicked the effects of PGE2. These data indicate that PGE2 acts primarily on the excitability of GABAergic presynaptic cells, most likely via alterations of voltage-gated K+ channels. Our results also suggest that far from being an inherent property of a specialized class of neurons, the degree of thermosensitivity can be strongly modulated by synaptic activity and is a more adaptive property of hypothalamic neurons than previously thought.