Serotonergic control of GABAergic inhibition in the lateral amygdala
Serotonergic control of GABAergic inhibition in the lateral amygdala
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外侧杏仁核中 GABA 能抑制的血清素控制
DOI：
10.1152/jn.00500.2019
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发表时间：
2020
影响因子：
2.5
通讯作者：
Kato Nobuo
中科院分区：
文献类型：
--
作者：
Yamamoto Ryo;Furuyama Takafumi;Sugai Tokio;Ono Munenori;Pare Denis;Kato Nobuo
许多证据表明杏仁核的多巴胺能调节与焦虑有关。因此，本研究采用离体全细胞记录技术，研究了5-羟色胺（5-HT）对大鼠杏仁外侧核（LA）主神经元（PNs）的影响。由于抑制是PN活性的主要决定因素，我们集中于5-HT对GABA能传递的控制。在谷氨酸受体拮抗剂的存在下，通过局部电刺激LA引起IPSC。我们发现5-HT通过突触前5-HT 1B受体减少GABA A抑制性突触后电流（IPSC）。虽然突触前抑制GABA的释放也减弱了GABA电流，但这种作用不如GABA电流明显，因为5-HT也诱导了GABA电流的竞争性突触后增强。也就是说，压力作用GABA或巴氯芬引起的GABAB电流被5-HT增强。此外，我们获得的证据表明，5-HT差异调节GABA能突触的不同子集。事实上，GABAAIPSC由两种成分组成：具有快速时程的相对5-HT不敏感的IPSC和具有较慢时程的5-HT敏感成分。由于这两种成分的相对贡献取决于神经元是在刺激电极附近还是在距离刺激电极一定距离处记录的，我们推测局部回路细胞的不同亚型贡献了两种GABA能突触。总的来说，我们的研究结果表明，5-HT是一个有效的调节突触抑制在LA。新&值得注意的是，我们报告说，5-HT，通过突触前5-HT 1B受体，减弱GABAIPSCs通过减少GABA释放在外侧杏仁核（LA）。与此同时，5-HT增强突触后GABAB电流，使得GABA抑制性突触后电流（IPSC）相对保留不受GABA释放的突触前抑制。我们还发现，5-HT敏感和不敏感的GABAAIPSCs的时间过程不同。总之，这些结果表明5-HT是LA中突触抑制的有效调节剂。
Much evidence implicates the serotonergic regulation of the amygdala in anxiety. Thus the present study was undertaken to characterize the influence of serotonin (5-HT) on principal neurons (PNs) of the rat lateral amygdala (LA), using whole cell recordings in vitro. Because inhibition is a major determinant of PN activity, we focused on the control of GABAergic transmission by 5-HT. IPSCs were elicited by local electrical stimulation of LA in the presence of glutamate receptor antagonists. We found that 5-HT reduces GABAAinhibitory postsynaptic currents (IPSCs) via presynaptic 5-HT1Breceptors. While the presynaptic inhibition of GABA release also attenuated GABABcurrents, this effect was less pronounced than for GABAAcurrents because 5-HT also induced a competing postsynaptic enhancement of GABABcurrents. That is, GABABcurrents elicited by pressure application of GABA or baclofen were enhanced by 5-HT. In addition, we obtained evidence suggesting that 5-HT differentially regulates distinct subsets of GABAergic synapses. Indeed, GABAAIPSCs were comprised of two components: a relatively 5-HT-insensitive IPSC that had a fast time course and a 5-HT-sensitive component that had a slower time course. Because the relative contribution of these two components varied depending on whether neurons were recorded at proximity versus at a distance from the stimulating electrodes, we speculate that distinct subtypes of local-circuit cells contribute the two contingents of GABAergic synapses. Overall, our results indicate that 5-HT is a potent regulator of synaptic inhibition in LA.NEW & NOTEWORTHYWe report that 5-HT, acting via presynaptic 5-HT1Breceptors, attenuates GABAAIPSCs by reducing GABA release in the lateral amygdala (LA). In parallel, 5-HT enhances GABABcurrents postsynaptically, such that GABABinhibitory postsynaptic currents (IPSCs) are relatively preserved from the presynaptic inhibition of GABA release. We also found that the time course of 5-HT-sensitive and -insensitive GABAAIPSCs differ. Together, these results indicate that 5-HT is a potent regulator of synaptic inhibition in LA.