Comparative Studies of Vocal Control

描述（由申请人提供）：参与鸟鸣控制的大脑区域的季节性生长和萎缩为研究与类固醇自然变化相关的神经元转换调节机制以及这种神经可塑性对感觉运动学习的功能后果提供了一个引人注目和独特的机会。在这个建议的目的解决神经可塑性的基本问题，特别是神经元的更新，在成人的大脑。这些包括类固醇激素和神经营养因子在神经元出生和死亡中的作用（目的1-2），神经营养因子在影响神经发生的神经元活动中的作用（目的3），以及在调节神经发生、神经元保护、死亡和活动的功能相关过程中重要的基因家族的协调表达（目的4）。鸟类鸣叫系统是研究神经可塑性的优秀模型；它是一个定义明确、易于处理的神经回路，显示出极端的季节性可塑性，并调节歌唱，这是一种易于分析的习得的感觉运动行为。这项研究将通过以下方式推进该领域的发展：1)阐明成人大脑中神经元出生和死亡之间功能联系的潜在机制（Aims 1,2）；2)提供神经营养因子影响歌唱系统神经元电生理的第一个证据（目标3）；3)通过将microRNA表达作为协调调节成人神经可塑性组成细胞过程的基因家族表达的分子机制进行分析，将这一领域超越单基因分析的水平（Aim 4）。

DESCRIPTION (provided by applicant): Seasonal growth and shrinkage of brain regions involved in control of birdsong provides a striking and unique opportunity to investigate the mechanisms regulating neuronal turnover associated with natural variation in steroids, and the functional consequences of this neural plasticity for sensorimotor learning. The aims in this proposal address fundamental issues of neural plasticity, and neuronal turnover in particular, in adult brains. These include the role of steroid hormones and neurotrophins in neuronal birth and death (Aims 1-2), the role of neurotrophins in neuronal activity that influences neurogenesis (Aim 3), and the coordinated expression of families of genes important in regulating functionally related processes of neurogenesis, neuronal protection, death, and activity (Aim 4). The birdsong system excels as a model for studies of neural plasticity; it is a well-defined and tractable neural circuit that shows extreme seasonal plasticity and regulates song, a learned sensorimotor behavior that is easily analyzed. This research will advance the field by 1) elucidating the mechanisms underlying the functional linkage between neuronal birth and death in adult brains (Aims 1,2); 2) providing the first evidence that neurotrophins influence the electrophysiology of neurons in the song system (Aim 3); 3) moving this field beyond the level of single gene analysis by opening up analysis of microRNA expression as a molecular mechanism for coordinating the expression of gene families that regulate the component cellular processes of adult neuroplasticity (Aim 4). PUBLIC HEALTH RELEVANCE: Steroid hormones have potential for use as neuroprotective agents in the treatment of stroke and a variety of neurodegenerative and mental health disorders. They are also of increasing concern as drugs of abuse. This work will examine the fundamental mechanisms by which these potent hormones influence neuronal birth, death, and gene expression.