Molecular Basis of a Critical Period in Cochlear Nucleus

描述（由申请人提供）：本研究的目的是确定可以定义小鼠脑干耳蜗核（CN）中外周输入丢失的显著易感性时期的分子机制。这一时期的基础和发展过程中的CN神经元生存独立于输入的开关基本上是未知的。这些研究将使用微阵列来鉴定在这一关键时期期间和之后表达水平变化的候选基因，以及鉴定在耳蜗消融去除输入后转录调节（诱导或抑制）的基因。基因改变的小鼠，可能与其他基因操作技术相结合，将用于研究选择的候选基因在耳蜗消融后CN神经元死亡和存活中的功能作用。这些研究还将检查第8神经活动在关键时期（小鼠听力开始前的一段时间）促进CN神经元存活的作用。随着人工耳蜗植入技术的发展，了解感觉剥夺和刺激返回对发育期和成年期中枢听觉神经元的影响，对于促进听觉功能的康复具有重要意义。

DESCRIPTION (provided by applicant): The goal of the present study is to identify the molecular mechanisms that could define a period of dramatic susceptibility to loss of peripheral input in the mouse brainstem cochlear nucleus (CN). The basis of this period and the switch during development to CN neuron survival independent of input is essentially unknown. These studies will use microarrays to identify candidate genes that change in level of expression during and after this critical period as well as to identify genes that are transcriptionally regulated (induced or repressed) following removal of input by cochlear ablation. Genetically altered mice, possibly in combination with other gene manipulation technologies, will be used to study the functional roles of selected candidate genes in death and survival of CN neurons following cochlear ablation. These studies will also examine the role of 8th nerve activity in promoting survival of CN neurons during the critical period, a time before the onset of hearing in mice. With recent advances in cochlear implant technologies, it is of great importance to understand the effects of sensory deprivation and the return of stimulation on central auditory neurons both during development and in adulthood in order to improve rehabilitation of auditory function.