Comparative Studies of Vocal Control

描述（由申请人提供）：鸟鸣控制相关脑区的季节性生长和收缩为研究与类固醇自然变异相关的神经元更新调节机制以及感觉运动学习神经可塑性的功能后果提供了一个引人注目的独特机会。这项建议的目的是解决神经可塑性的基本问题，特别是成年人大脑中的神经元周转。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）。鸟鸣系统作为神经可塑性研究的模型表现出色;它是一个定义明确且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面推动这一领域的发展：1）阐明成年人大脑中神经元出生和死亡之间的功能联系的机制（目的1，2）提供神经营养因子影响鸣唱系统神经元电生理的第一个证据（目的3）;第三章通过将microRNA表达分析作为协调基因表达的分子机制，调节成人神经可塑性组成细胞过程的家族（目的4）。 公共卫生相关性：类固醇激素有可能作为神经保护剂用于治疗中风和各种神经退行性疾病和精神健康疾病。它们作为滥用药物也日益受到关注。这项工作将研究这些强效激素影响神经元出生，死亡和基因表达的基本机制。

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.