Hippocampal interneurons are excited via serotonin-gated ion channels
Hippocampal interneurons are excited via serotonin-gated ion channels
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DOI：
10.1152/jn.1997.78.5.2493
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发表时间：
1997-11-01
影响因子：
2.5
通讯作者：
Kauer, JA
中科院分区：
文献类型：
--
作者：
McMahon, LL;Kauer, JA
中缝核的血清素能神经元大量支配位于 CA1 区放射层的海马 GABA 能中间神经元，表明这种强烈的皮质下投射可能调节中间神经元的兴奋性。利用脑切片中中间神经元的全细胞膜片钳记录，我们测试了血清素 (5-HT) 对这些中间神经元生理特性的影响。当突触传递被河豚毒素和钴阻断时，血清素会产生快速的内向电流，该电流持续存在，并且不受离子型谷氨酸和γ-氨基丁酸（GABA）受体拮抗剂的影响。 5-HT 诱导电流与 G 蛋白激活无关。药理学证据表明，5-HT 通过激活 5-HT3 受体直接兴奋这些中间神经元。在膜电位为负至 -55 mV 时，5-HT 电流的电流-电压 (I-V) 关系显示出负斜率电导区域。因此，中间神经元对 5-HT 的反应强烈依赖于膜电位，并且随着细胞去极化而大大增加。去除细胞外钙，但不去除镁，会增加 5-HT 感应电流的幅度，并去除负斜率电导区域，从而使 I-V 关系线性化。 5-HT 反应性中间神经元的轴突在 CA1 内广泛分支；其中一些中间神经元还投射到齿状回并在齿状回中广泛形成树状结构。这些抑制性连接的组织强烈表明这些细胞调节 CA1 锥体细胞和齿状颗粒细胞的兴奋性。我们的结果表明 5-HT 可能介导这些中间神经元的快速兴奋性突触传递，血清素能输入可以同时调节海马和齿状回的输出。
Serotonergic neurons of the median raphe nucleus heavily innervate hippocampal GABAergic interneurons located in stratum radiatum of area CA1, suggesting that this strong subcortical projection may modulate interneuron excitability. Using whole cell patch-clamp recording from interneurons in brain slices, we tested the effects of serotonin (5-HT) on the physiological properties of these interneurons. Serotonin produces a rapid inward current that persists when synaptic transmission is blocked by tetrodotoxin and cobalt, and is unaffected by ionotropic glutamate and gamma-aminobutyric acid (GABA) receptor antagonists. The 5-HT-induced current was independent of G-protein activation. Pharmacological evidence indicates that 5-HT directly excites these interneurons through activation of 5-HT3 receptors. At membrane potentials negative to -55 mV, the current-voltage (I-V) relationship of the 5-HT current displays a region of negative slope conductance. Therefore the response of interneurons to 5-HT strongly depends on membrane potential and increases greatly as cells are depolarized. Removal of extracellular calcium, but not magnesium, increases the amplitude of 5-HT-induced currents and removes the region of negative slope conductance, thereby linearizing the I-V relationship. The axons of 5-HT-responsive interneurons ramify widely within CA1; some of these interneurons also project to and arborize extensively in the dentate gyrus. The organization of these inhibitory connections strongly suggests that these cells regulate excitability of both CA1 pyramidal cells and dentate granule cells. As our results indicate that 5-HT may mediate fast excitatory synaptic transmission onto these interneurons, serotonergic inputs can simultaneously modulate the output of both hippocampus and dentate gyrus.