Plasticity of Vocal Control

声音控制的可塑性

• 批准号: 6695629
• 负责人: ELIOT A BRENOWITZ
• 金额: $ 11.79万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6695629
• 关键词: animal communication behavior; behavioral /social science research tag; gene expression; gene targeting; genetic mapping; hormone regulation /control mechanism; in situ hybridization; learning; molecular cloning; neural plasticity; neuroanatomy; neuroendocrine system; polymerase chain reaction; psychobiology; songbirds; steroid hormone; vocalization

DESCRIPTION (provided by applicant): The long-term goal of this research is to understand the neuroendocrine basis of behavior used in communication. The birdsong system is a valuable model because song is learned, and its neural circuits are sexually dimorphic, hormone sensitive, and plastic in adults. Seasonal plasticity of the song control system provides an especially interesting model of plasticity in vertebrate brains, and a continuing goal of this research program is to understand the mechanisms and functional consequences of these seasonal changes. The immediate goal of this application is to receive training in methods of molecular biology that will enable the candidate to extend his studies of plasticity of the song system to a molecular level of analysis. Brenowitz will learn gene cloning, mapping and targeting, single and double-label in situ hybridization, PCR, and nonviral cRNA transfection methods in the laboratory of Robert Steiner at the University of Washington (UW). The candidate will be trained by Paul Neiman of the Fred Hutchison Cancer Research Center in Seattle in the use of eDNA microarrays to analyze patterns of gene expression, and in bioinformatic methods for data analysis. Brenowitz will take a course on microarray analysis at the UW Center for Expression Arrays. Scott Edwards of UW will train Brenowitz in DNA sequencing methods. The candidate will "apprentice" at the Institute for Systems Biology in Seattle to learn current methods of proteomics and bioinformatics. UW has a strong research program, with particular strengths in birdsong, endocrinology, neuroscience, molecular biology, animal behavior, and hearing research. The candidate's appointments in the Depts. of Psychology, Zoology, and the Bloedet Hearing Research Center provide access to shared facilities that benefit his research program. The proposed research will address mechanisms and functional consequences of seasonal plasticity in the song system. Aims 1 & 2, will test the hypotheses that social enhancement of seasonal growth is mediated by auditory cues and involves increased neuronal recruitment. Aim 3 will test the hypothesis that afferent innervation is necessary to maintain seasonally grown song nuclei. Aim 4 will test the hypothesis that seasonal growth of song circuits is mediated by estrogenic metabolites of testosterone. Aim 5 will use operant conditioning to test the hypothesis that seasonal plasticity of the song nuclei causes seasonal changes in song perception. Aim 6 will use in situ hybridization to test the hypothesis that expression of the gene for brain derived neurotrophic factor is upregulated when the song circuits are seasonally growing. Aim 7 will use subtractive suppressive hybridization to identify genes that are enriched in a song nucleus that grows seasonally compared with a nucleus that does not grow. Aim 8 will use a customized eDNA microarray to analyze global patterns of gene expression that are associated with seasonal growth of the telencephalic song control circuits. The results of the proposed studies will increase our understanding of the influences of steroid hormones and social stimuli on the nervous system, and the relationship between plasticity in the adult brain and learning.

描述（由申请人提供）：这项研究的长期目标是了解交流中使用的行为的神经内分泌基础。 Birdsong系统是一个有价值的模型，因为学习了歌曲，并且其神经回路具有性二态，激素敏感和成人的塑料。歌曲控制系统的季节性可塑性为脊椎动物大脑提供了特别有趣的可塑性模型，该研究计划的持续目标是了解这些季节性变化的机制和功能后果。该应用的直接目标是接受分子生物学方法的培训，这将使候选人能够将歌曲系统的可塑性扩展到分子分析水平。 Brenowitz将在华盛顿大学罗伯特·施泰纳（Robert Steiner）实验室（UW）学习基因克隆，映射和靶向，单位和双标记原位杂交，PCR和非病毒CRNA转染方法。候选人将由西雅图弗雷德·哈奇森癌研究中心的Paul Neiman培训，用于使用Edna微阵列来分析基因表达的模式，并在生物信息学方法中进行数据分析。 Brenowitz将在UW表达阵列中心进行微阵列分析课程。 UW的Scott Edwards将以DNA测序方法训练Brenowitz。候选人将在西雅图系统生物学研究所“学徒”学习当前的蛋白质组学和生物信息学方法。 UW具有强大的研究计划，在鸟鸣，内分泌学，神经科学，分子生物学，动物行为和听力研究方面具有特殊优势。候选人在部门任命。心理学，动物学和Bloedet听力研究中心的掌握提供了对他的研究计划有利的共享设施的访问权限。拟议的研究将解决歌曲系统中季节性可塑性的机制和功能后果。 AIMS 1和2将检验以下假设：季节性增长的社会增长是由听觉提示介导的，并涉及增加神经元募集。 AIM 3将检验以下假设：维持季节性成长的歌曲核必须需要传入。 AIM 4将检验以下假设：歌曲电路的季节性生长是由睾丸激素的雌激素代谢物介导的。 AIM 5将使用操作调节来检验以下假设：歌曲核的季节性可塑性会导致歌曲感知的季节性变化。 AIM 6将使用原位杂交来检验以下假设：当歌曲电路在季节性增长时，基因的表达在脑衍生的神经营养因子上被上调。 AIM 7将使用减法抑制杂交来识别与不生长的核相比，富含季节性的歌曲核中富集的基因。 AIM 8将使用自定义的EDNA微阵列来分析与尾脑歌曲控制电路季节性生长有关的基因表达的全球模式。拟议的研究的结果将增加我们对类固醇激素和社会刺激对神经系统的影响的理解，以及成人大脑中的可塑性与学习之间的关系。