Primary afferent activation of thermosensitive TRPV1 triggers asynchronous glutamate release at central neurons.

Primary afferent activation of thermosensitive TRPV1 triggers asynchronous glutamate release at central neurons.
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DOI:
10.1016/j.neuron.2010.02.017
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发表时间:
2010-03-11
期刊:
影响因子:
16.2
通讯作者:
Andresen, Michael C.
Andresen, Michael C.
中科院分区:
医学1区
文献类型:
--
作者:
Peters, James H.;McDougall, Stuart J.;Fawley, Jessica A.;Smith, Stephen M.;Andresen, Michael C.

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TRPV 1受体在脊髓初级传入的伤害性感受中具有显著特征,但也在与稳态调节相关的无髓鞘颅内脏初级传入中表达。颅内脏传入神经在孤束核(NTS)进入大脑,以控制心脏、肺和其他重要器官。在这里,我们确定了一个新的作用,中央TRPV 1在活动依赖性的促进孤束(ST)传入的多巴胺能传递。辣椒素敏感(TRPV 1+)和不敏感(TRPV 1 −)传入的快速同步ST-NTS传输是相似的。然而,传入激活触发长期持续的异步谷氨酸释放TRPV 1+突触。异步释放与同步EPSC振幅、活动和钙离子进入成正比。TRPV 1拮抗剂和低温阻断非同步释放,但不诱发EPSC。在生理传入频率,异步释放强烈增强突触后尖峰的持续时间。这种活性依赖性TPRV 1介导的易化是一种新形式的突触可塑性,为CNS和自主调节带来了独特的中枢整合特征。
TRPV1 receptors feature prominently in nociception of spinal primary afferents but are also expressed in unmyelinated cranial visceral primary afferents linked to homeostatic regulation. Cranial visceral afferents enter the brain at the solitary tract nucleus (NTS) to control the heart, lungs and other vital organs. Here we identify a novel role for central TRPV1 in the activity-dependent facilitation of glutamatergic transmission from solitary tract (ST) afferents. Fast, synchronous ST-NTS transmission from capsaicin sensitive (TRPV1+) and insensitive (TRPV1−) afferents was similar. However, afferent activation triggered long lasting asynchronous glutamate release only from TRPV1+ synapses. Asynchronous release was proportional to synchronous EPSC amplitude, activity, and calcium entry. TRPV1 antagonists and low temperature blocked asynchronous release but not evoked EPSCs. At physiological afferent frequencies, asynchronous release strongly potentiated the duration of postsynaptic spiking. This activity dependent TPRV1-mediated facilitation is a novel form of synaptic plasticity that brings a unique central integrative feature to the CNS and autonomic regulation.
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