The cellular code for mammalian thermosensation.
The cellular code for mammalian thermosensation.
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DOI：
10.1523/jneurosci.5788-12.2013
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发表时间：
2013-03-27
期刊：
影响因子：
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通讯作者：
Hoon MA
中科院分区：
文献类型：
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作者：
Pogorzala LA;Mishra SK;Hoon MA
哺乳动物的躯体感觉神经元对热刺激作出反应，使动物能够可靠地区分冷热并选择它们喜欢的环境。我们先前通过在发育早期切除几种不同类型的伤害感受器，产生了对从有害的寒冷到痛苦的高温（-5至55 °C）的温度完全不敏感的小鼠。在这里，我们采用了一种选择性消融策略，在成年小鼠解剖这种表型，从而证明了分子定义的神经元的不同群体对热和冷的反应。表达TRPV 1的神经元负责对40至50°C之间的温度的所有行为反应，而TRPM 8神经元则是厌恶寒冷所必需的。我们还表明，更极端的冷和热激活伤害感受器，包括表达Mrgprd的细胞的额外群体。因此，尽管单独消除Mrgprd神经元不会影响对温度的行为反应，但当与TRPV 1或TRPM 8细胞的消融相结合时，它分别显着降低了对极热和极冷的反应。值得注意的是，TRPM 8-神经元的消融扭曲了对优选温度的反应，这表明温暖的舒适热感觉实际上可能只是反映了TRPM 8和TRPV 1-神经元的厌恶输入减少。正如这一假设所预测的那样，缺乏这两类热敏元件的小鼠对10至50 °C之间的温度既不表现出厌恶反应，也不表现出吸引反应。总之，这些结果提供了一个简单的细胞基础哺乳动物的温度感觉，其中两个分子定义类的感觉神经元检测和编码的吸引力和厌恶的线索。
Mammalian somatosenory neurons respond to thermal stimuli allowing animals to reliably discriminate hot from cold and select their preferred environments. We previously generated mice that are completely insensitive to temperatures from noxious cold to painful heat (−5 to 55 °C) by ablating several different classes of nociceptor early in development. Here we have adopted a selective ablation strategy in adult mice to dissect this phenotype and thereby demonstrated that separate populations of molecularly defined neurons respond to hot and cold. TRPV1-expressing neurons are responsible for all behavioral responses to temperatures between 40 and 50°C, while TRPM8-neurons are required for cold aversion. We also show that more extreme cold and heat activate additional populations of nociceptors including cells expressing Mrgprd. Thus, although eliminating Mrgprd-neurons alone does not affect behavioral responses to temperature, when combined with ablation of TRPV1- or TRPM8-cells, it significantly decreases responses to extreme heat and cold respectively. Notably, ablation of TRPM8-neurons distorts responses to preferred temperatures suggesting that the pleasant thermal sensation of warmth may in fact just reflect reduced aversive-input form TRPM8 and TRPV1-neurons. As predicted by this hypothesis, mice lacking both these classes of thermosensor exhibited neither aversive nor attractive responses to temperatures between 10 and 50 °C. Taken together these results provide a simple cellular basis for mammalian thermosensation whereby two molecularly defined classes of sensory neurons detect and encode both attractive and aversive cues.