Regulation of leptin receptor-expressing neurons in the brainstem by TRPV1.
Regulation of leptin receptor-expressing neurons in the brainstem by TRPV1.
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DOI：
10.14814/phy2.12160
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发表时间：
2014-09-01
影响因子：
2.5
通讯作者：
Derbenev AV
中科院分区：
文献类型：
--
作者：
Zsombok A;Jiang Y;Gao H;Anwar IJ;Rezai-Zadeh K;Enix CL;Münzberg H;Derbenev AV
中枢神经系统通过控制内脏器官的自主输出，在摄食行为和全身代谢的调节中起着关键作用。迷走神经背侧运动核（DMV）中的副交感神经元的活动决定迷走神经张力，从而调节脑下器官的功能。瘦素高度参与食物摄入的调节并改变脑干神经元的神经元兴奋性。瞬时受体电位香草酸1型（TRPV 1）也被证明可以增加脑干中的神经传递，我们测试了TRPV 1调节突触前神经递质释放到表达瘦素受体（LepRbEGFP）的DMV神经元的假设。进行全细胞膜片钳记录以确定TRPV 1激活对DMV中LepRbEGFP神经元的兴奋性和抑制性突触后电流（EPSC，IPSC）的影响。辣椒素，一种TRPV 1激动剂，增加了50%的LepRbEGFP神经元中微型EPSC的频率，而不改变DMV中微型IPSC的频率。使用跨突触逆行病毒示踪剂PRV-614在DMV中鉴定胃投射LepRbEGFP神经元。TRPV 1的激活增加了约50%的胃相关LepRbEGFP DMV神经元中mEPSC的频率。这些数据表明，TRPV 1通过突触前机制增加兴奋性神经传递到LepRbEGFP DMV神经元的亚群，并表明TRPV 1和DMV中的瘦素信号传导之间的潜在相互作用。e12160我们的数据表明TRPV 1通过突触前机制参与迷走神经背侧运动核中瘦素受体表达神经元亚群的调节。
The central nervous system plays a critical role in the regulation of feeding behavior and whole‐body metabolism via controlling the autonomic output to the visceral organs. Activity of the parasympathetic neurons in the dorsal motor nucleus of the vagus (DMV) determines the vagal tone and thereby modulates the function of the subdiaphragmatic organs. Leptin is highly involved in the regulation of food intake and alters neuronal excitability of brainstem neurons. Transient receptor potential vanilloid type 1 (TRPV1) has also been shown to increase neurotransmission in the brainstem and we tested the hypothesis that TRPV1 regulates presynaptic neurotransmitter release to leptin receptor‐expressing (LepRbEGFP) DMV neurons. Whole‐cell patch‐clamp recordings were performed to determine the effect of TRPV1 activation on excitatory and inhibitory postsynaptic currents (EPSC, IPSC) of LepRbEGFP neurons in the DMV. Capsaicin, a TRPV1 agonist increased the frequency of miniature EPSCs in 50% of LepRbEGFP neurons without altering the frequency of miniature IPSCs in the DMV. Stomach‐projecting LepRbEGFP neurons were identified in the DMV using the transsynaptic retrograde viral tracer PRV‐614. Activation of TRPV1 increased the frequency of mEPSC in ~50% of stomach‐related LepRbEGFP DMV neurons. These data demonstrate that TRPV1 increases excitatory neurotransmission to a subpopulation of LepRbEGFP DMV neurons via presynaptic mechanisms and suggest a potential interaction between TRPV1 and leptin signaling in the DMV. e12160 Our data demonstrate that TRPV1 is involved in the regulation of a subpopulation of leptin receptor‐expressing neurons in the dorsal motor nucleus of the vagus via presynaptic mechanisms.