TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus.

TRPV1 regulates excitatory innervation of OLM neurons in the hippocampus.
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DOI:
10.1038/ncomms15878
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发表时间:
2017-07-19
影响因子:
16.6
通讯作者:
Dean C
Dean C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Hurtado-Zavala JI;Ramachandran B;Ahmed S;Halder R;Bolleyer C;Awasthi A;Stahlberg MA;Wagener RJ;Anderson K;Drenan RM;Lester HA;Miwa JM;Staiger JF;Fischer A;Dean C

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TRPV 1是由热和刺激剂(包括辣椒素)激活的离子通道,并且已经在感觉神经元的伤害感受中被广泛研究。然而,TRPV 1在海马中的位置和功能仍有争议。我们发现TRPV 1在海马的定向-腔隙-分子(OLM)中间神经元中表达,并促进兴奋性神经支配。TRPV 1基因敲除小鼠OLM神经元的多巴胺能神经支配减少。当被辣椒素激活时,TRPV 1在体外招募更多的多巴胺能而不是GABA能终末到OLM神经元。当TRPV 1被阻断时,OLM神经元的多巴胺能输入显著减少。TRPV 1的异源表达也增加兴奋性神经支配。此外,TRPV 1基因敲除降低了Schaffer侧支LTP,这是通过用尼古丁激活OLM神经元(通过含α2β2的烟碱受体)来绕过神经支配缺陷而挽救的。我们的研究结果揭示了TRPV 1在海马中特定的中间神经元群体中的突触发生功能,在那里它对于门控海马可塑性很重要。TRPV 1在CNS中的作用尚未完全了解。在这里,作者表明TRPV 1在海马的生长抑素阳性OLM中间神经元中特异性表达,在那里它促进这些细胞的兴奋性神经支配。
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. The role of TRPV1 in the CNS is not fully understood. Here the authors show that TRPV1 is expressed specifically in somatostatin-positive OLM interneurons of the hippocampus, where it promotes excitatory innervation of these cells.
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