Comparative Studies of Vocal Control

描述(申请人提供)：参与鸟鸣控制的大脑区域的季节性生长和收缩为研究与类固醇自然变化相关的神经元更新的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惊人而独特的机会。这项建议的目的是解决神经可塑性的基本问题，特别是成年大脑中的神经元更替。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(目标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(目标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(目标4)。鸟鸣系统非常适合作为研究神经可塑性的模型；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，并调节歌声，这是一种易于分析的习得感觉运动行为。这项研究将通过以下方式推动该领域的发展：1)阐明成人大脑中神经元出生和死亡之间潜在的功能联系的机制(目标1，2)；2)首次提供神经营养因子影响SONG系统神经元电生理的证据(目标3)；3)通过打开对microRNA表达的分析，将这一领域超越单基因分析的水平，将其作为协调基因家族表达的分子机制，这些基因家族调节成人神经可塑性的组成细胞过程(目标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).