Role of the afterhyperpolarization in control of discharge properties of septal cholinergic neurons in vitro
Role of the afterhyperpolarization in control of discharge properties of septal cholinergic neurons in vitro
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DOI：
10.1152/jn.1996.75.2.695
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发表时间：
1996-02-01
影响因子：
2.5
通讯作者：
Reiner, PB
中科院分区：
文献类型：
--
作者：
Gorelova, N;Reiner, PB
1. 采用膜片钳全细胞记录的方法，研究了大鼠中隔和布洛卡斜带核（MS/DBB）胆碱能神经元的性质。用荧光亲和素和内源性胆碱乙酰转移酶分别观察56个MS/DBB神经元细胞内沉积的生物胞素和内源性胆碱乙酰转移酶的递质表型和膜特性。28个MS/DBB神经元中有27个在单动作电位和异常矫正后表现出明显的慢后超极化（sAHP）。其余28个神经元表现出其他固有的膜特性，没有一个神经元具有胆碱乙酰转移酶免疫反应性。MS/DBB胆碱能神经元的sAHP可通过减少细胞外钙或添加100 μ M镉而被可逆阻断，并可通过30 nM的维生素胺而被不可逆阻断，这表明sAHP是由维生素胺敏感的钙活化钾电导产生的。MS/DBB胆碱能神经元在sAHP之前也表现出峰后去极化后电位（DAP）。当细胞外钙含量降低以及10-50 μ M NiCl2存在时，DAP和sAHP均被阻断。应用500 nM ω - concontoxin也降低了sAHP，同时保持DAP完整。这些数据表明瞬态和高阈值钙电导都有助于sahp的产生。当去极化时，胆碱能神经元放电缓慢（2-4 Hz），且有规律，几乎没有证据表明有峰值频率适应。当多巴胺阻断sAHP时，瞬时放电频率增加，神经元表现出明显的峰值频率适应。5-羟色胺（5-HT）可逆转抑制MS/DBB胆碱能神经元的sAHP，并改变其放电模式，从缓慢的规则放电转变为适度的峰值频率适应。由此可见，sAHP限制了MS/DBB胆碱能神经元的放电速率，5-HT对sAHP的生理相关抑制可能导致MS/DBB胆碱能神经元放电模式的状态依赖性改变。
1. The properties of the cholinergic neurons of the rat medial septum and nucleus of the diagonal band of Broca (MS/DBB) were studied using whole cell patch-clamp recordings in an in vitro slice preparation.2. Both the transmitter phenotype and the intrinsic membrane properties of 56 MS/DBB neurons were determined post hoc by visualizing intracellularly deposited biocytin with fluorescent avidin and endogenous choline acetyltransferase with immunofluorescence. Twenty seven of 28 MS/DBB neurons exhibiting both a prominent slow afterhyperpolarization (sAHP) following a single action potential and anomalous rectification were identified as cholinergic. The remaining 28 neurons exhibited other intrinsic membrane properties and none were choline acetyltransferase immunoreactive.3. The sAHP in MS/DBB cholinergic neurons was blocked reversibly either by reducing extracellular calcium or addition of 100 mu M cadmium and irreversibly blocked by 30 nM apamin, suggesting that the sAHP is produced by an apamin-sensitive calcium-activated potassium conductance.4. MS/DBB cholinergic neurons also exhibited a postspike depolarizing afterpotential (DAP) preceeding the sAHP. Both the DAP and the sAHP were blocked when extracellular calcium was lowered as well as in the presence of 10-50 mu M NiCl2. Application of 500 nM omega-conotoxin also reduced the sAHP, while leaving the DAP intact. These data suggest that both transient and high-threshold calcium conductances contribute to generation of the sAHP.5. When depolarized, cholinergic neurons fired slowly (2-4 Hz) and regularly with little evidence of spike frequency adaptation. When the sAHP was blocked with apamin, the instantaneous frequency of firing increased and the neuron now exhibited prominent spike frequency adaptation.6. Serotonin (5-HT) reversibly suppressed the sAHP in MS/DBB cholinergic neurons and altered the firing pattern from slow regular discharge to one which exhibited modest spike frequency adaptation.7. It was concluded that the sAHP Limits the firing rate of MS/DBB cholinergic neurons and that physiologically relevant supression of the sAHP by 5-HT may result in state-dependent changes in the discharge pattern of MS/DBB cholinergic neurons.