Gamkrelidze G, Giaume C, Peusner K D
Department of Anatomy and Cell Biology, and Neuroscience Program, George Washington University Medical Center, Washington, DC 20037, USA.
J Neurosci. 1998 Feb 15;18(4):1449-64. doi: 10.1523/JNEUROSCI.18-04-01449.1998.
The principal cells of the chick tangential nucleus are second-order sensory neurons that participate in the three-neuron vestibulo-ocular and vestibulocollic reflexes. In postnatal animals, second-order vestibular neurons fire repetitively on depolarization. Previous studies have shown that, although this is an important feature for normal reflex function, it is only acquired gradually during embryonic development. Whereas at 13 embryonic days (E13) the principal cells accommodate after firing a single spike, at E16 a few principal cells repetitively can fire multiple action potentials on depolarization. Finally, in the hatchling, the vast majority of principal cells is capable of nonaccommodating firing on depolarization. As a first step in understanding the mechanisms underlying developmental change in excitability of these second-order vestibular neurons, we analyzed the outward potassium currents and their role in accommodation, using brainstem slices at E16. The principal cells exhibited transient and sustained potassium currents, with both of these containing calcium-dependent components. Further, both high- and low-threshold sustained potassium currents have been distinguished. The low-threshold dendrotoxin-sensitive sustained potassium current (IDS) is associated with principal cells that accommodate and is not expressed in those that fire repetitively. Finally, blocking of IDS transforms accommodating cells into neurons capable of firing trains of action potentials on depolarization. These findings indicate that suppression of IDS during development is sufficient to transform accommodating principal cells into nonaccommodating firing neurons and suggests that developmental regulation of this current is necessary for the establishment of normal vestibular function.
鸡切线核的主要细胞是参与三神经元前庭眼反射和前庭颈反射的二级感觉神经元。在出生后的动物中,二级前庭神经元在去极化时会重复放电。先前的研究表明,尽管这是正常反射功能的一个重要特征,但它在胚胎发育过程中是逐渐获得的。在胚胎第13天(E13)时,主要细胞在发放单个动作电位后会出现适应性变化,而在E16时,少数主要细胞在去极化时能够重复发放多个动作电位。最后,在幼雏中,绝大多数主要细胞在去极化时能够进行非适应性发放。作为理解这些二级前庭神经元兴奋性发育变化潜在机制的第一步,我们使用E16期的脑干切片分析了外向钾电流及其在适应性变化中的作用。主要细胞表现出瞬时和持续的钾电流,两者都包含钙依赖性成分。此外,还区分了高阈值和低阈值的持续钾电流。低阈值的树突毒素敏感的持续钾电流(IDS)与具有适应性变化的主要细胞相关,而在能够重复发放动作电位的细胞中不表达。最后,阻断IDS会将具有适应性变化的细胞转变为在去极化时能够发放动作电位序列的神经元。这些发现表明,发育过程中IDS的抑制足以将具有适应性变化的主要细胞转变为非适应性发放的神经元,并提示该电流的发育调节对于建立正常的前庭功能是必要的。