Serotoninergic dorsal raphe neurons possess functional postsynaptic nicotinic acetylcholine receptors
Serotoninergic dorsal raphe neurons possess functional postsynaptic nicotinic acetylcholine receptors
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DOI：
10.1002/syn.20526
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发表时间：
2008-08-01
期刊：
影响因子：
2.3
通讯作者：
Mihailescu, Stefan
中科院分区：
文献类型：
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作者：
Galindo-Charles, Luis;Hernandez-Lopez, Salvador;Mihailescu, Stefan
端脑中很少有神经元表达功能性突触后烟碱乙酰胆碱受体（nAChR），其中包括去甲肾上腺素能和多巴胺能神经元。然而，没有证据表明突触后nAChRs对多巴胺能神经元。在这项研究中，我们问，如果功能nAChRs是目前在中缝背核（DRN）的多巴胺能（5-HT）和非多巴胺能（非5-HT）神经元。在大鼠中脑脑片上，场刺激被盖脚桥核（PPT）诱发DRN神经元不同成分的突触后电流（eEPSC）。在阻断谷氨酸能和GABA能成分后，剩余的eEPSC被美加明阻断，并被选择性α 7 nAChR拮抗剂甲基乌头碱（MLA）或选择性α 4 β 2 nAChR拮抗剂二氢-β-eritroidine（DH β E）还原。同时添加MLA和DHPE阻断了所有eEPSC。PPT-DRN通路的完整性通过顺行生物胞素示踪和来自DRN的逆向刺激来评估。在阿托品和河豚毒素的存在下，直接应用乙酰胆碱（ACh）诱发的内向电流由两种动力学不同的电流组成：一种被MLA阻断，另一种被DH β E阻断;在5-HT和非5-HT DR神经元中。自发（sEPSC）和诱发（eEPSC）突触事件的分析得出的结论是，nAChR位于突触后膜。这些新描述的nAChRs在各种生理过程和行为事件，如觉醒-睡眠周期的可能影响进行了讨论。
Very few neurons in the telencephalon have been shown to express functional postsynaptic nicotinic acetylcholine receptors (nAChRs), among them, the noradrenergic and dopaminergic neurons. However, there is no evidence for postsynaptic nAChRs on serotonergic neurons. In this study, we asked if functional nAChRs are present in serotonergic (5-HT) and nonserotonergic (non-5-HT) neurons of the dorsal raphe nucleus (DRN). In rat midbrain slices, field stimulation at the tegmental pedunculopontine (PPT) nucleus evoked postsynaptic currents (eEPSCs) with different components in DRN neurons. After blocking the glutamatergic and GABAergic components, the remaining eEPSCs were blocked by mecamylamine and reduced by either the selective alpha 7 nAChR antagonist methyllycaconitine (MLA) or the selective alpha 4 beta 2 nAChR antagonist dihydro-beta-eritroidine (DH beta E). Simultaneous addition of MLA and DHPE blocked all eEPSCs. Integrity of the PPT-DRN pathway was assessed by both anterograde biocytin tracing and antidromic stimulation from the DRN. Inward currents evoked by the direct application of acetylcholine (ACh), in the presence of atropine and tetrodotoxin, consisted of two kinetically different currents: one was blocked by MLA and the other by DH beta E; in both 5-HT and non-5-HT DR neurons. Analysis of spontaneous (sEPSCs) and evoked (eEPSCs) synaptic events led to the conclusion that nAChRs were located at the postsynaptic membrane. The possible implications of these newly described nAChRs in various physiological processes and behavioral events, such as the wake-sleep cycle, are discussed.