Seasonal Plasticity in Steroid-Sensitive Neural Circuits

类固醇敏感神经回路的季节性可塑性

• 批准号: 6750644
• 负责人: Gregory F Ball
• 金额: $ 30.21万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-08 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6750644
• 关键词: androgen receptor; animal communication behavior; antisense nucleic acid; behavioral /social science research tag; biological signal transduction; brain derived neurotrophic factor; catecholamines; corpus striatum; gene induction /repression; glycoproteins; hormone regulation /control mechanism; neural plasticity; neural recruitment; neuroanatomy; neurogenesis; neuropsychology; neuroregulation; photostimulus; regulatory gene; seasons; songbirds; testosterone; tyrosine 3 monooxygenase; vocalization

DESCRIPTION (provided by applicant): Understanding brain plasticity is a major challenge facing the neurosciences. One class of animal models useful for these studies involves brain changes that occur naturally in response to salient environmental stimuli that regulate seasonal variation in reproductive physiology. Seasonal changes in the brain of songbirds are one of the most dramatic examples of this natural neuroplasticity. This proposal analyzes the anatomical circuits and cellular events that mediate the effects of steroid hormones on singing behavior and on the morphological plasticity of song control nuclei and investigates the possible effects of singing on brain plasticity. Aim I will determine whether steroids act directly on neurons that are active during singing (Expt 1). Aim II concerns the role of catecholamines in song production by analyzing the relationships among tyrosine hydroxylase-immunoreactive inputs to song control nuclei, immediate early gene expression (IEG) and steroid receptors (Expts 2-4). Aims III and IV will investigate steroid controls of cellular signals that are implicated in the recruitment and survival of new neurons that contribute to seasonal changes in the brain. Aim III will analyze whether steroids act directly on cells that produce Brain Derived Neurotrophic Factor (BDNF) and will investigate the effects of singing on BDNF expression in song nuclei (Expts 5-6). Exp 7 will test with antisense techniques whether singing-induced IEG expression is required for the stimulaton of BDNF production. Reelin, a glycoprotein that plays a key role in neuronal positioning during ontogeny, was recently shown to be present and regulated by testosterone (T) in song nucleus HVc in adult birds. Aim IV will explore the role of reelin in the recruitment of new neurons into HVc by determining whether reelin receptors are present in newborn HVc neurons (Expt 8), characterizing the effects of T on reelin expression (Expts 9-12) and assessing the effects on neuronal incorporation of manipulations of reelin expression (Expt 13). Aim V (expt 14) will investigate whether the seasonal dissociations between the effects of T on song and on the growth of song control nuclei can be explained by the uncoupling of the response to T of some of the cellular responses investigated in the initial phases of the project. These studies will provide an integrated view of cellular mechanisms that mediate song expression and the associated seasonal neuroplasticity and will contribute to an understanding of whether brain changes can be mediated via changes in behavioral expression.

描述（由申请人提供）：了解大脑可塑性是神经科学面临的主要挑战。对这些研究有用的一类动物模型涉及大脑的变化，这些变化是自然发生的，以响应调节生殖生理学季节性变化的显著环境刺激。鸣禽大脑的季节性变化是这种天然神经可塑性的最引人注目的例子之一。本研究分析了类固醇激素对歌唱行为和歌唱控制核团形态可塑性影响的解剖学回路和细胞事件，并研究了歌唱对大脑可塑性的可能影响。目的研究类固醇激素是否直接作用于歌唱时活跃的神经元。目的II通过分析向鸣唱控制核团的酪氨酸羟化酶免疫反应性输入、立即早期基因表达（IEG）和类固醇受体之间的关系，关注儿茶酚胺在鸣唱产生中的作用（实验2-4）。目的III和IV将研究类固醇对细胞信号的控制，这些信号与促进大脑季节性变化的新神经元的招募和存活有关。目的III分析类固醇是否直接作用于产生脑源性神经营养因子（BDNF）的细胞，并研究歌唱对歌唱核团BDNF表达的影响（实验5-6）。实验7将用反义技术测试是否需要歌唱诱导的IEG表达来刺激BDNF的产生。Reelin是一种在个体发育过程中对神经元定位起关键作用的糖蛋白，最近被证明存在于成年鸟类的鸣唱核HVc中，并受睾酮（T）的调节。目的IV将通过确定新生HVc神经元中是否存在reelin受体（实验8）、表征T对reelin表达的影响（实验9-12）和评估操纵reelin表达对神经元掺入的影响（实验13）来探索reelin在新生神经元募集到HVc中的作用。目的V（实验14）将研究T对歌曲和对歌曲控制核团生长的影响之间的季节性分离是否可以通过该项目初始阶段研究的一些细胞反应对T的反应的解偶联来解释。这些研究将提供介导歌曲表达和相关季节性神经可塑性的细胞机制的综合观点，并有助于理解大脑变化是否可以通过行为表达的变化来介导。