NICOTINIC ACTIVITY DEPRESSES SYNAPTIC POTENTIATION IN LAYER V PYRAMIDAL NEURONS OF MOUSE INSULAR CORTEX
NICOTINIC ACTIVITY DEPRESSES SYNAPTIC POTENTIATION IN LAYER V PYRAMIDAL NEURONS OF MOUSE INSULAR CORTEX
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DOI：
10.1016/j.neuroscience.2017.06.031
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发表时间：
2017-09-01
期刊：
影响因子：
3.3
通讯作者：
Toyoda, Hiroki
中科院分区：
文献类型：
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作者：
Sato, Hajime;Kawano, Tsutomu;Toyoda, Hiroki
岛叶皮质是尼古丁成瘾的关键脑区。然而，尼古丁成瘾的具体细胞和突触机制在很大程度上仍不清楚。在本研究中，我们研究了尼古丁如何调节小鼠岛叶皮质V层锥体神经元的突触传递和可塑性。我们还研究了在岛叶皮质的第V层，哪种类型的神经元表达功能性烟碱型乙酰胆碱受体(NAChRs)。我们发现尼古丁抑制由突触前刺激和突触后去极化(配对训练)相结合而引起的突触增强。尼古丁显著增强自发兴奋性突触后电流(EPSCs)和抑制性突触后电流(IPSCs)：前者是通过激活含有β2的nAChRs介导的，而后者主要是通过激活含有β2的nAChRs介导的，少量是通过激活含有α7的nAChRs介导的。尼古丁可显著增强诱发的IPSCs，但对诱发的EPSCs无影响。我们还发现，在小鼠岛叶皮质的V层，大多数非快峰(Non-FS)中间神经元具有含有β2的nAChRs，而大约一半的锥体神经元和FS中间神经元具有功能性nAChRs。阻断GABA(A)受体或含有β2的nAChRs可阻止尼古丁对突触增强的影响。综上所述，这些结果表明，在岛叶皮质的V层锥体神经元中，非FS中间神经元表达的含有β2的nAChRs的激活通过促进GABA能突触传递而抑制突触增强。这些发现为尼古丁成瘾中岛叶皮质变化的细胞和突触机制提供了重要的见解。(C)2017 IBRO。爱思唯尔有限公司出版。保留所有权利。
The insular cortex is a critical brain region involved in nicotine addiction. However, its specific cellular and synaptic mechanisms underlying nicotine addiction remains largely unknown. In the present study, we examined how nicotine modulates synaptic transmission and plasticity in layer V pyramidal neurons of the mouse insular cortex. We also examined which type of neurons express functional nicotinic acetylcholine receptors (nAChRs) in layer V of the insular cortex. We found that nicotine suppresses synaptic potentiation induced by combination of presynaptic stimulation with postsynaptic depolarization (paired training). An application of nicotine significantly enhanced both spontaneous excitatory postsynaptic currents (EPSCs) and inhibitory postsynaptic currents (IPSCs): the former effect was mediated by activation of beta 2-containing nAChRs while the latter one was mediated largely by activation of beta 2-containing nAChRs and to a minor extent by activation of alpha 7-containing nAChRs. The application of nicotine significantly enhanced evoked IPSCs but had no effect on evoked EPSCs. We also found that in layer V of the mouse insular cortex, majority of non-fast-spiking (non-FS) interneurons have beta 2-containing nAChRs while about half of pyramidal neurons and FS interneurons have functional nAChRs. Blockade of GABA(A) receptors or beta 2-containing nAChRs prevented the effects of nicotine on synaptic potentiation. Taken together, these results suggest that in layer V pyramidal neurons of the insular cortex, activation of beta 2-containing nAChRs expressed in non-FS interneurons suppresses synaptic potentiation through enhancing GABAergic synaptic transmission. These findings provide important insights into the cellular and synaptic mechanisms of insular cortical changes in nicotine addiction.(C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.