Intrinsic membrane properties underlying spontaneous tonic firing in neostriatal cholinergic interneurons
Intrinsic membrane properties underlying spontaneous tonic firing in neostriatal cholinergic interneurons
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DOI：
10.1523/jneurosci.20-22-08493.2000
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发表时间：
2000-11-15
影响因子：
5.3
通讯作者：
Wilson, CJ
中科院分区：
文献类型：
--
作者：
Bennett, BD;Callaway, JC;Wilson, CJ
新纹状体胆碱能中间神经元在没有突触输入的情况下产生自发的紧张性放电。穿孔斑片记录和全细胞记录结合钙成像在体外被用来识别内源性兴奋性的内在膜特性。自发放电是由钠电流和超极化激活的阳离子电流(i-h)共同作用驱动的，这两者共同确保了在亚阈值电压范围内没有零电流点。阻断钠通道或I-h建立了稳定的亚阈值静息膜电位。在约-60 mV和阈值(约-50 mV)之间观察到河豚毒素的负斜率电导敏感区域，并且在所有阈值电压下都激活h-电流。钙成像实验表明，在阈值下膜电位有少量的钙内流，但动作电位引起胞体和树突中钙的升高。尖峰触发的钙内流改变了动作电位波形的下降相，并激活了钙依赖钾通道。大电导通道的阻断导致了棘波的展宽。应用阿帕明阻断小电导通道，消除慢峰后超极化(AHP)并引起向爆发式放电的转变。在没有突触输入的情况下，观察到一系列紧张性放电模式，表明体内记录的强直活动胆碱能神经元(TAN)的特征峰电位序列是内在起源的。AHP在调节棘波模式中的关键作用表明，体内TAN的爆发式放电可能是由AHP的直接或间接调制引起的，而不需要时相突触输入。
Neostriatal cholinergic interneurons produce spontaneous tonic firing in the absence of synaptic input. Perforated patch recording and whole-cell recording combined with calcium imaging were used in vitro to identify the intrinsic membrane properties underlying endogenous excitability. Spontaneous firing was driven by the combined action of a sodium current and the hyperpolarization-activated cation current (I-h), which together ensured that there was no zero current point in the subthreshold voltage range. Blockade of sodium channels or I-h established a stable subthreshold resting membrane potential. A tetrodotoxin-sensitive region of negative slope conductance was observed between approximately -60 mV and threshold (approximately -50 mV) and the h-current was activated at all subthreshold voltages.Calcium imaging experiments revealed that there was minimal calcium influx at subthreshold membrane potentials but that action potentials produced elevations of calcium in both the soma and dendrites. Spike- triggered calcium entry shaped the falling phase of the action potential waveform and activated calcium-dependent potassium channels. Blockade of big-conductance channels caused spike broadening. Application of apamin, which blocks small-conductance channels, abolished the slow spike afterhyperpolarization (AHP) and caused a transition to burst firing.In the absence of synaptic input, a range of tonic firing patterns are observed, suggesting that the characteristic spike sequences described for tonically active cholinergic neurons (TANs) recorded in vivo are intrinsic in origin. The pivotal role of the AHP in regulating spike patterning indicates that burst firing of TANs in vivo could arise from direct or indirect modulation of the AHP without requiring phasic synaptic input.