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. Although TRPV1 receptors are mainly found in nociceptive neurons of the peripheral nervous system, these receptors have also been found in the brain, where their role is far less understood. Activation of TRPV1 reportedly regulates neurotransmitter release at several central synapses. However, we found that TRPV1 suppressed excitatory transmission in rat and mouse dentate gyrus by regulating postsynaptic function in an input-specific manner. This suppression was a result of Ca2+-calcineurin and clathrin-dependent internalization of AMPA receptors. Moreover, synaptic activation of TRPV1 triggered 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 previously unknown form of endocannabinoid- and TRPV1-mediated regulation of synaptic strength at central synapses.
机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Tominaga, M
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Caterina, MJ
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机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Caterina, MJ
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Malmberg, AB
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机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Malmberg, AB
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Rosen, TA
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机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Rosen, TA
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Gilbert, H
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机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Gilbert, H
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Skinner, K
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机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Skinner, K
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Raumann, BE
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机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Raumann, BE
;
Basbaum, AI
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机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Basbaum, AI
;
Julius, D
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机构:
Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Tominaga, M
;
Caterina, MJ
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Caterina, MJ
;
Malmberg, AB
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Malmberg, AB
;
Rosen, TA
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Rosen, TA
;
Gilbert, H
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Gilbert, H
;
Skinner, K
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Skinner, K
;
Raumann, BE
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Raumann, BE
;
Basbaum, AI
论文数: 0引用数: 0
h-index: 0
机构:Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA
Basbaum, AI
;
Julius, D
论文数: 0引用数: 0
h-index: 0
机构:
Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USAUniv Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA