GABAA receptors increase excitability and conduction velocity of cerebellar parallel fiber axons
GABAA receptors increase excitability and conduction velocity of cerebellar parallel fiber axons
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DOI：
10.1152/jn.01028.2011
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发表时间：
2012-06-01
影响因子：
2.5
通讯作者：
Otis, Thomas S.
中科院分区：
文献类型：
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作者：
Dellal, Shlomo S.;Luo, Ray;Otis, Thomas S.
Dellal SS，Luo R，奥蒂斯TS. GABA（A）受体增加小脑平行纤维轴突的兴奋性和传导速度。J Neurophysiol 107：2958-2970，2012.首次发表于2012年2月29日; doi：10.1152/jn.01028.2011.-在成年哺乳动物脑中，GABA（A）受体（GABA（A）Rs）负责突触抑制的主要形式，但当氯平衡电位（E-Cl）去极化时，这些受体可兴奋神经元。在许多成熟神经元中，GABA（A）受体位于突触前末梢，在那里发挥去极化作用。为了了解兴奋性GABA的作用是否影响轴突功能，我们使用小脑横切片测量笼状GABA的光解对复合平行纤维（PF）动作电位（AP）的起始和传播的影响。笼状GABA的光解增加了PF AP的幅度和传导速度; GABA再摄取阻断剂和GABA（A）Rs的正性调节剂增强了这些作用。相反，对含有δ-亚基的GABA（A）Rs具有选择性的调节剂没有增强这些作用，并且在δ（-/-）小鼠中保持了反应性，这表明不需要含有δ-亚基的GABA（A）Rs。突触释放的GABA也增加PF兴奋性，表明该机制是由生理信号。构建了PF轴突和颗粒细胞体的Hodgkin-Huxley式房室模型，该模型概括了GABA依赖性AP阈值降低和传导速度增加，这些特征对E-Cl和钠通道失活的电压依赖性敏感。该模型还预测，轴突GABA（A）Rs可以影响顺向锋电位的起始。我们的结论是，GABA作用于小脑PF有利于穗的产生和传播，使颗粒细胞的轴突被动地整合信号从抑制性中间神经元和影响信息流的输入层小脑皮质。
Dellal SS, Luo R, Otis TS. GABA(A) receptors increase excitability and conduction velocity of cerebellar parallel fiber axons. J Neurophysiol 107: 2958-2970, 2012. First published February 29, 2012; doi:10.1152/jn.01028.2011.-In the adult mammalian brain, GABA(A) receptors (GABA(A)Rs) are responsible for the predominant forms of synaptic inhibition, but these receptors can excite neurons when the chloride equilibrium potential (E-Cl) is depolarized. In many mature neurons, GABA(A)Rs are found on presynaptic terminals where they exert depolarizing effects. To understand whether excitatory GABA action affects axonal function, we used transverse cerebellar slices to measure the effects of photolysis of caged GABA on the initiation and propagation of compound parallel fiber (PF) action potentials (APs). Photolysis of caged GABA increased the amplitude and conduction velocity of PF APs; GABA reuptake blockers and a positive modulator of GABA(A)Rs enhanced these effects. In contrast, a modulator selective for delta-subunit-containing GABA(A)Rs did not enhance these effects and responsiveness remained in delta(-/-) mice, arguing that delta-subunit-containing GABA(A)Rs are not required. Synaptically released GABA also increased PF excitability, indicating that the mechanism is engaged by physiological signals. A Hodgkin-Huxley-style compartmental model of the PF axon and granule cell body was constructed, and this model recapitulated the GABA-dependent decrease in AP threshold and the increase in conduction velocity, features that were sensitive to E-Cl and to the voltage dependence of sodium channel inactivation. The model also predicts that axonal GABA(A)Rs could affect orthodromic spike initiation. We conclude that GABA acting on cerebellar PFs facilitates both spike generation and propagation, allowing axons of granule cells to passively integrate signals from inhibitory interneurons and influence information flow in the input layer to the cerebellar cortex.