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TRPV1 调节海马中 OLM 神经元的兴奋性神经支配。

TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus.

机构信息

Trans-synaptic Signaling Group, European Neuroscience Institute, Grisebachstrasse 5, Goettingen 37077, Germany.

Department of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Robert Koch Strasse 40, Göttingen 37075, Germany.

出版信息

Nat Commun. 2017 Jul 19;8:15878. doi: 10.1038/ncomms15878.

DOI:10.1038/ncomms15878
PMID:28722015
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5524938/
Abstract

TRPV1 is an ion channel activated by heat and pungent agents including capsaicin, and has been extensively studied in nociception of sensory neurons. However, the location and function of TRPV1 in the hippocampus is debated. We found that TRPV1 is expressed in oriens-lacunosum-moleculare (OLM) interneurons in the hippocampus, and promotes excitatory innervation. TRPV1 knockout mice have reduced glutamatergic innervation of OLM neurons. When activated by capsaicin, TRPV1 recruits more glutamatergic, but not GABAergic, terminals to OLM neurons in vitro. When TRPV1 is blocked, glutamatergic input to OLM neurons is dramatically reduced. Heterologous expression of TRPV1 also increases excitatory innervation. Moreover, TRPV1 knockouts have reduced Schaffer collateral LTP, which is rescued by activating OLM neurons with nicotine-via α2β2-containing nicotinic receptors-to bypass innervation defects. Our results reveal a synaptogenic function of TRPV1 in a specific interneuron population in the hippocampus, where it is important for gating hippocampal plasticity.

摘要

TRPV1 是一种被热和辛辣物质（包括辣椒素）激活的离子通道，在感觉神经元的伤害感受中被广泛研究。然而，TRPV1 在海马体中的位置和功能存在争议。我们发现 TRPV1 在海马体的齿状回门区-腔隙分子层（OLM）中间神经元中表达，并促进兴奋性神经支配。TRPV1 敲除小鼠的 OLM 神经元谷氨酸能神经支配减少。当被辣椒素激活时，TRPV1 在体外将更多的谷氨酸能，但不是 GABA 能，末梢募集到 OLM 神经元。当 TRPV1 被阻断时，OLM 神经元的谷氨酸能输入显著减少。TRPV1 的异源表达也增加了兴奋性神经支配。此外，TRPV1 敲除小鼠的 Schaffer 侧支长时程增强（LTP）减少，通过用尼古丁激活 OLM 神经元（通过含有 α2β2 的烟碱型受体）绕过神经支配缺陷，可挽救这种减少。我们的结果揭示了 TRPV1 在海马体中特定中间神经元群体中的突触发生功能，这对门控海马体可塑性很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/41220819c04e/ncomms15878-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/107ed391e569/ncomms15878-f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/351e6bff27b0/ncomms15878-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/41220819c04e/ncomms15878-f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/107ed391e569/ncomms15878-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/8bac83219d18/ncomms15878-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/0c084e0b9d8b/ncomms15878-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/7aa6c9376181/ncomms15878-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/5b7681a7c051/ncomms15878-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/ddf28c9e6b6b/ncomms15878-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/d0caee6bf04c/ncomms15878-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/351e6bff27b0/ncomms15878-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5085/5524938/41220819c04e/ncomms15878-f9.jpg

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