TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus.

TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus.
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DOI:
10.1038/nn.2684
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发表时间:
2010-12
影响因子:
25
通讯作者:
Castillo, Pablo E.
Castillo, Pablo E.
中科院分区:
医学1区
文献类型:
--
作者:
Chavez, Andres E.;Chiu, Chiayu Q.;Castillo, Pablo E.

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瞬时受体电位TRPV 1是介导疼痛感觉的非选择性阳离子通道,通常由各种外源性和内源性、物理和化学刺激激活。虽然TRPV 1受体主要存在于外周神经系统的伤害感受神经元中,但这些受体也在脑中被描述,其中它们的作用远未被理解。据报道,TRPV 1的激活调节几个中枢突触的神经递质释放。然而,在这里,我们表明,TRPV 1抑制大鼠和小鼠齿状回的兴奋性传递,通过调节突触后功能的输入特定的方式。这种抑制是由于AMPA受体的Ca 2 +-钙调神经磷酸酶和网格蛋白依赖性内化。此外,TRPV 1的突触激活触发了一种由内源性大麻素anandamide以1型大麻素受体非依赖性方式介导的长期抑制(TRPV 1-LTD)。因此,我们的研究结果揭示了一种新形式的内源性大麻素和TRPV 1介导的调节突触强度在中央突触。
The transient receptor potential TRPV1 is a nonselective cation channel that mediates pain sensations and is commonly activated by a wide variety of exogenous and endogenous, physical and chemical stimuli. While TRPV1 receptors are mainly found in nociceptive neurons of the peripheral nervous system, these receptors have also been described in the brain where their role is far less understood. Activation of TRPV1 reportedly regulates neurotransmitter release at several central synapses. Here we show, however, that TRPV1 suppresses excitatory transmission in rat and mouse dentate gyrus by regulating postsynaptic function in an input-specific manner. This suppression is due to a Ca2+-calcineurin and clathrin-dependent internalization of AMPA receptors. Moreover, synaptic activation of TRPV1 triggers a form of long-term depression (TRPV1-LTD) mediated by the endocannabinoid anandamide in a type 1 cannabinoid receptor-independent manner. Thus, our findings reveal a novel form of endocannabinoid- and TRPV1-mediated regulation of synaptic strength at central synapses.
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