Regulation of firing response gain by calcium-dependent mechanisms in vestibular nucleus neurons
Regulation of firing response gain by calcium-dependent mechanisms in vestibular nucleus neurons
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DOI：
10.1152/jn.00821.2001
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发表时间：
2002-04-01
影响因子：
2.5
通讯作者：
Du Lac, S
中科院分区：
文献类型：
--
作者：
Smith, MR;Nelson, AB;Du Lac, S
行为反射可以通过在很大程度上未知的机制被经验改变。在前庭眼球反射(VOR)回路中，前庭内侧核(MVN)神经元表现出与VOR增益(诱发眼速与输入头部速度之比)相关的放电频率反应的适应性变化。虽然突触强度的变化通常被认为是VOR增益变化的基础，但决定放电的内在离子通道的调制也可能起到作用。然而，关于离子通道功能或调节如何影响MVN神经元的放电反应，人们知之甚少。本研究探讨了钙依赖电流对啮齿动物脑干脑片全细胞贴片记录的MVN神经元放电反应的影响。在很宽的射速范围内，发射反应都是非常线性的，并且表现出适度的尖峰频率适应。放电反应增益，即诱发放电频率与输入电流之比，随细胞外钙浓度的增加而降低，但可通过降低细胞外钙离子浓度或拮抗SK和BK型钙依赖钾通道和Nand T型钙通道而增加。阻断SK通道通过N型钙通道闭塞增益增加，而阻断BK通道通过假定的T型钙通道闭塞增益增加，表明钾通道与其钙来源的特异性偶联。选择性抑制钙/钙调蛋白依赖的激酶II和广谱抑制磷酸酶通过BK依赖的途径调节增益，表明放电反应受到严格调控。通过磷酸化来调节激发反应增益为VOR增益的自适应控制提供了一种有吸引力的机制。
Behavioral reflexes can be modified by experience via mechanisms that are largely unknown. Within the circuitry for the vestibuloocular reflex (VOR), neurons in the medial vestibular nucleus (MVN) show adaptive changes in firing rate responses that are correlated with VOR gain (the ratio of evoked eye velocity to input head velocity). Although changes in synaptic strength are typically assumed to underlie gain changes in the VOR, modulation of intrinsic ion channels that dictate firing could also play a role. Little is known, however, about how ion channel function or regulation contributes to firing responses in MVN neurons. This study examined contributions of calcium-dependent currents to firing responses in MVN neurons recorded with whole cell patch electrodes in rodent brain stem slices. Firing responses were remarkably linear over a wide range of firing rates and showed modest spike frequency adaptation. Firing response gain, the ratio of evoked firing rate to input current, was reduced by increasing extracellular calcium and increased either by lowering extracellular calcium or with antagonists to SK- and BK-type calcium-dependent potassium channels and Nand T-type calcium channels. Blockade of SK channels occluded gain increases via N-type calcium channels, while blocking BK channels occluded gain increases via presumed T-type calcium channels, indicating specific coupling of potassium channels and their calcium sources. Selective inhibition of Ca2+/calmodulin-dependent kinase II and broad-spectrum inhibition of phosphatases modulated gain via BK-dependent pathways, indicating that firing responses are tightly regulated. Modulation of firing response gain by phosphorylation provides an attractive mechanism for adaptive control of VOR gain.