RECOVERY OF VESTIBULAR FUNCTION DURING REGENERATION

描述（由申请人提供）：头部运动时的凝视稳定是一种复杂的行为反应，高度依赖于前庭系统的功能。事实上，前庭损伤通常会导致平衡和凝视障碍。值得注意的是，鸟类在损伤后表现出深刻的自发前庭受体再生。然而，最近的研究结果表明，与病变前相比，前庭介导的包括凝视在内的眼睛和头部成分的反应在再生后显著不同。这些发现表明，前庭神经机制的注视控制响应运动已被修改在再生。为了了解前庭功能是如何在损伤后恢复的，该项目将检查初级前庭传入事件和辅助凝视的中央核神经元的生理学。实验旨在扩展我们对前庭受体形态再生发育的广泛知识。例如，已知受体传入再生的时间序列为三阶段，其中钮扣纤维首先恢复，其次是二形态，然后是花萼传入。完成后，再生传入的大部分地形组织复制正常的形态发生表型。然而，再生的神经支配模式明显不同于正常纤维，神经支配结构不那么复杂。接下来的问题是这些形态差异如何影响运动信息的神经处理。在Specific Aim 1中，将在受体再生的三个独特阶段获得前庭传入反应对运动的神经生理学记录。在这些研究中，我们将研究传入反应在其重新发展过程中的空间和时间特性。此外，我们将研究空间区分阈值，以精细运动方向的差异。特异性目标2将检查中央前庭神经元，专门控制眼睛和头部凝视行为的组成部分。在再生的三个阶段，神经生理学记录将被执行在已识别的神经元上，这些神经元要么投射到脊髓，要么与眼动有关。基于先前的行为凝视研究，我们预计前庭脊髓神经元将早日恢复对运动的反应，以稳定头部。随后，眼动相关神经元将恢复对运动的反应。具体目标3将根据其放电规律解决两类事件的贡献的相关问题。先前的研究表明，有规律的放电传入主要参与眼球运动的控制，而不规则的放电传入更多地参与头部稳定。通过利用一种可逆的方法，电流沉默不规则发射传入，规则和不规则纤维对凝视的相对贡献将被检查。

DESCRIPTION (provided by applicant): Gaze stabilization during head motion is a complex behavioral response that is highly dependent upon a functioning vestibular system. In fact, vestibular insult often results in balance and gaze disorders. Remarkably, birds demonstrate profound spontaneous vestibular receptor regeneration following damage. However, recent findings have demonstrated that the vestibular mediated eye and head component responses that comprise gaze differ significantly following regeneration as compared to pre-lesion conditions. These findings suggest that the vestibular neural mechanisms underlying gaze control in response to motion have been modified during regeneration. In an effort to understand how vestibular functions recover following damage, the proposed project will examine the physiology of primary vestibular afferents and central nuclei neurons that sub-serve gaze. Experiments are designed to expand upon our extensive knowledge of the regarding the morphological regenerative development of vestibular receptors. For example, it is known that a tri-staged temporal sequence of receptor afferent regeneration occurs, in which bouton fibers recover first, followed by dimorph, then calyx afferents late. When complete, much of the topographic organization of regenerated afferents reproduced that of the normal morphogenetic phenotype. However, the regenerated innervation patterns differed significantly from normal fibers having less complex innervation structures. The question is then raised as to how these morphologic differences affect neural processing of motion information. In Specific Aim 1, neurophysiological recordings of vestibular afferent responses to motion will be obtained during the three unique stages of receptor regeneration. In these studies, we will examine the spatial and temporal properties of afferent responses during their re-development. In addition, we will examine spatial discrimination thresholds to fine differences in motion direction. Specific Aim 2 will examine the central vestibular neurons that specifically control the eye and head components of gaze behavior. Neurophysiological recordings will be performed on identified neurons that project either to the spinal cord or are eye movement related during the three stages of regeneration. Based upon previous behavioral gaze studies, we expect that vestibulospinal neurons will regain their response to motion early in order to stabilize the head. Later, eye movement related neurons will regain their response to motion. Specific Aim 3 will address a related issue of the contribution of two classes of afferents based upon their discharge regularity. Previous studies have suggested that regular firing afferents are primarily involved in control of eye movements while irregular firing afferents are more involved in head stabilization. By utilizing a reversible method of galvanic silencing of irregular firing afferents, the relative contributions of regular and irregular fibers toward gaze will be examined. PUBLIC HEALTH RELEVANCE: Although the vestibuloocular reflex (VOR) is one of the most well understood neural systems in the brain, much less is known regarding the complimentary function of VOR, vestibulocollic reflex (VCR), and cervicocollic reflex (CCR) responses to adequately control gaze behavior. In addition our knowledge regarding the functional recovery of the neural substrates underlying the gaze compensation following vestibular receptor damage remains lacking. The current project seeks to Increase our fundamental understanding of the afferent, central vestibular neuron, and gaze behavior response recovery process, which is essential, before more effective treatments of vestibular system disorders can be realized.