Opposing electrophysiological actions of 5-HT on noncholinergic and cholinergic neurons in the rat ventral pallidum in vitro
Opposing electrophysiological actions of 5-HT on noncholinergic and cholinergic neurons in the rat ventral pallidum in vitro
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DOI：
10.1152/jn.00543.2003
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发表时间：
2004-07-01
影响因子：
2.5
通讯作者：
Osborne, PB
中科院分区：
文献类型：
--
作者：
Bengtson, CP;Lee, DJ;Osborne, PB
大鼠腹侧苍白球是前脑的一个基底结构，包含投射到边缘系统纹状体苍白球回路的神经元和大细胞胆碱能皮质脑神经元。由于中缝背核投射上的5-羟色胺（5-HT）终末与这些神经元形成紧密的并置，我们在未成熟大鼠脑片上进行了膜片钳记录，以确定它们是否受到突触后5-HT受体的调节。内向电流主要由5-HT诱导的非胆碱能神经元，这是区分从胆碱能神经元的免疫组织化学和电生理标准。当用毛喉素刺激腺苷酸环化酶时，5-HT诱导的内向电流被模仿和阻断，当用铯阻断非胆碱能神经元的h电流时，5-HT诱导的内向电流几乎被取消。与cAMP在其他脑区激活5-HT 7受体的h电流一致，我们发现内向电流被混合的5-HT 1/ 5-HT 7激动剂5-甲氧基色胺和5-羧酰胺色胺（5-CT）模拟，5-CT比5-HT更有效。与此相反，5-HT 1偏好8-OH-DPAT是一个弱的部分激动剂，5-HT 1选择性拮抗剂吲哚洛尔没有效果。然而，尽管有这种情况，在5-HT 7受体结合的拮抗剂仅部分减少激动剂内向电流（SB-269970和氯氮平），或没有效果（米安色林和匹莫齐特）。我们发现，在胆碱能神经元，5- HT主要诱导超极化电流，这是由钾通道，并小于8-OH-DPAT和5-CT诱导的电流。我们的结论是，从中缝背侧上升5- HT的预测可能有直接和相反的影响，在边缘系统的纹状体和胆碱能皮质回路腹侧苍白球内的神经元的活动。
The ventral pallidum in rat is a basal forebrain structure that contains neurons that project in the limbic striatopallidal circuitry and magnocellular cholinergic corticopetal neurons. Because 5-hydroxytryptamine (5-HT) terminals on dorsal raphe projections form close appositions with these neurons, we made patch- clamp recordings in immature rat brain slices to determine whether they are modulated by postsynaptic 5-HT receptors. Inward currents were predominantly induced by 5-HT in noncholinergic neurons, which were distinguished from cholinergic neurons by immunohistochemical and electrophysiological criteria. The inward current induced by 5-HT was mimicked and occluded when adenylyl cyclase was stimulated with forskolin, and was almost abolished when h-currents in noncholinergic neurons were blocked with cesium. Consistent with 5-HT7 receptor activation of h-curents by cAMP in other brain regions, we found inward currents were mimicked by the mixed 5-HT1/ 5-HT7 agonists 5-methoxytryptamine, and by 5-carboxamidotryptamine (5-CT), which was more potent than 5-HT. In contrast, 5-HT1 preferring 8-OH-DPAT was a weak partial agonist, and the 5-HT1 -selective antagonist pindolol had no effect. However, despite this profile, antagonists that bind at the 5-HT7 receptor only partly reduced the agonist inward current (SB-269970 and clozapine), or had no effect ( mianserin and pimozide). We found in cholinergic neurons that 5- HT predominantly induced hyperpolarizing currents, which were carried by potassium channels, and were smaller than currents induced by 8-OH-DPAT and 5-CT. We conclude from this study that ascending 5- HT projections from the dorsal raphe could have direct and opposite effects on the activities of neurons within the limbic striatopallidal and cholinergic corticopetal circuitry in the ventral pallidum.