AFFERENT INFLUENCES ON AUDITORY SYSTEM ONTOGENY

要了解正常和异常脑发育的基本原理，就需要了解细胞事件的知识，而不同的经历正是通过这些细胞事件影响神经结构和功能的个体发育。 在听觉系统，这一领域的研究取得了新的和直接的临床重要性，越来越多的使用人工耳蜗植入先天性和语前听力受损的婴儿。 该申请寻求继续资助一项研究计划，旨在了解内耳完整性和活动对脑干听觉通路发育的影响的细胞事件。将继续或启动四项独立的调查。1.我们将继续调查的假设，细胞内钙稳态起着关键作用，在调节事件的启动，导致transneuronal细胞死亡的年轻动物内耳损伤或剥夺声学驱动的内耳活动。 2.我们将研究一个特定的分子，钾通道（Kv1.1），被认为在听觉信息的时间编码中发挥独特的重要作用的活动依赖性调节。该分子表达的传入调节将在基因转录、蛋白质和耳蜗核细胞功能特性的水平上进行检查。 3.我们将使用正常和突变小鼠来研究发育和成熟大脑对剥夺诱导的退化的不同易感性的生物学原理。 4.我们将结合联合收割机单细胞标记、电生理和钙离子成像等方法来研究树突结构传入调节的细胞机制。

Understanding the fundamental principles of normal and abnormal brain development requires knowledge of the cellular events whereby differential experience influences the ontogeny of neural structure and function. In the auditory system, this area of research has achieved new and immediate clinical importance with the increasing use of cochlear implants in congenitally and prelingually hearing impaired infants. This application seeks continued funding for a research program aimed at understanding the cellular events underlying the influence of inner ear integrity and activity on development of brainstem auditory pathways. Four separate lines of investigation will be either continued or initiated. 1. We will continue to investigate the hypothesis that intracellular calcium homeostasis plays a key role in regulating the initiation of events leading to transneuronal cell death of brainstem neurons in young animals following damage to the inner ear or deprivation of acoustically driven inner ear activity. 2. We will investigate activity-dependent regulation of a specific molecule, a potassium channel (Kv1.1), thought to play a uniquely important role in the temporal coding of auditory information. Afferent regulation of the expression of this molecule will be examined at the levels of gene transcription, protein, and functional properties of cochlear nucleus cells. 3. We will use normal and mutant mice to examine the biological principles underlying differential susceptibility of the developing and mature brains to deprivation-induced degeneration. 4. We will combine single cell labeling, electrophysiology and calcium imaging methods to study the cellular mechanisms of afferent regulation of dendritic structure.