RECOVERY FOLLOWING DAMAGE TO THE VESTIBULAR SYSTEM

单侧功能丧失后出现的部分功能恢复 前庭功能的一种变化称为“前庭补偿”。“这 中枢神经系统可塑性的一个显著例子发生在 天虽然补偿的功能范围经常被 高估，其最突出的特点，消除前庭 眼球震颤似乎取决于对称活动的恢复， 前庭次级传入位于双侧前庭 原子核。这种对称放电的恢复不需要依赖于 复杂的神经网络特性。而是前庭代偿 可能反映了活动依赖性神经元的自我调节。如果辅助 前庭传入活动呈现不对称，那么最终 对称性可以通过突触活性依赖性表达来建立， 转运蛋白或受体;调节突触后 对许多变送器系统的灵敏度。拟议的研究具有 目的是了解亚细胞机制， “赔偿。“同样的机制也可能解释了 在正常刺激条件下观察前庭可塑性。 该建议将：1）确定亚细胞机制， 与单侧脑缺血后功能恢复相关 在大鼠和家兔中均行睾丸切除术。我们将用免疫细胞化学 和特异性突触受体、转运蛋白 生长相关蛋白43（GAP-43）和亚细胞信使， 蛋白激酶C（PKC）。我们将研究初级传入神经 前庭传入投射到前庭核和小脑 结节以及通向下橄榄核的次级前庭通路 和网状核。2)实验区分 退化和再生引发的机制之间的联系 前庭神经，而不是增加的机制， 神经活动减少这可以通过比较 单侧睾丸切除术引起的效应， 单侧外淋巴注射耳毒性氨基糖苷类药物， 链霉素。链霉素注射会使前庭原发性 传入神经完好无损我们还将比较单方面 具有长期视动效应的视网膜切除术 刺激.这种刺激引起的眼球震颤相当于 单侧眼震的严重程度和持续时间 子宫切除术。3)开发小脑、前庭、 兔的下橄榄、橄榄、下橄榄、橄榄、下橄榄、下橄榄、橄榄之一 试图调查特定发射机的技术困难 在任何特定物种中使用任一寡核苷酸的途径是， 感兴趣的基因可能已经为不同的物种克隆 （通常是老鼠）。然而， 前庭系统以兔脑最为著名。我们所采取的方法 建议重点是组织化学、分子和生物化学 技术对物种的生理功能是最容易的 研究了建议的实验将导致更好的理解 前庭代偿的重要分子参与者。

The partial recovery of function that occurs following a unilateral loss of vestibular function is termed "vestibular compensation." This remarkable example of central nervous system plasticity occurs within days. Although the functional extent of compensation has frequently been overestimated, its most prominent feature, the elimination of vestibular nystagmus appears to depend on the restoration of symmetrical activity of vestibular secondary afferents located bilaterally in the vestibular nuclei. This restoration of symmetrical discharge need not depend on complicated neuronal network properties. Rather vestibular compensation may reflect activity-dependent neuronal self-regulation. If secondary vestibular afferent activity is rendered asymmetrical, then eventually symmetry could be established by activity-dependent expression of synaptic transporters or receptors; molecules that regulate the postsynaptic sensitivity for many transmitter systems. The proposed research has the objective of understanding the subcellular mechanisms that contribute to "compensation." These same mechanisms might also account for the vestibular plasticity observed under normal stimulus conditions. This proposal will: 1) Determine the subcellular mechanisms that are correlated with recovery of function following a unilateral labyrinthectomy in both rats and rabbits. We will use immunocytochemical and oligonucleotide probes for specific synaptic receptors , transporters , growth associated protein-43 (GAP-43), and the subcellular messenger, protein kinase C (PKC). We will investigate the primary afferent vestibular afferent projections to the vestibular nuclei and cerebellar nodulus, as well as secondary vestibular pathways to the inferior olive and nucleus reticularis gigantocellularis. 2) Distinguish experimentally between mechanisms triggered by degeneration and regeneration of the vestibular nerve as opposed to mechanisms that are triggered by increases and decreases in neural activity. This can be achieved by comparing the effects induced by unilateral labyrinthectomy with the effects produced by a unilateral perilymphatic injection of an ototoxic aminoglycoside, such as streptomycin. The streptomycin injection would leave vestibular primary afferents intact. We will also compare the effects of unilateral labyrinthectomy with effects that are induced by long-term optokinetic stimulation. Such stimulation induces a nystagmus that is equivalent in both severity and duration to the nystagmus induced by unilateral labyrinthectomy. 3) Develop cDNA libraries of the cerebellum, vestibular complex, Scarpa's ganglion and inferior olive of the rabbit. One of the technical difficulties in trying to investigate transmitter-specific pathways using either oligonucleotide in any particular species is that the genes of interest may have been cloned for a different species (usually the rat or mouse). However, the functional physiology of the vestibular system is best known for the rabbit brain. The approach that we propose would focus are histochemical, molecular and biochemical techniques on the species for which physiological function is most easily investigated. The proposed experiments will lead to a better understanding of the important molecular participants in vestibular compensation.