Steroid Hormone Regulation of Brain Plasticity and Vocal Behavior

类固醇激素对大脑可塑性和声音行为的调节

• 批准号: 9886292
• 负责人: Gregory F Ball
• 金额: $ 29.02万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9886292
• 关键词: Ablation; Address; Adult; Anatomy; Androgens; Animals; Area; Aromatase; Basic Science; Behavior; Behavioral; Birds; Brain; Breeding; Cell Nucleus; Cells; Clinical Research; Comparative Study; Complex; Crystallization; Development; Dimensions; Elements; Endogenous Factors; Environmental Risk Factor; Enzymes; Estrogens; Extracellular Matrix; Extracellular Structure; Female; Follow-Up Studies; Gene Expression; Goals; Hormones; Immediate-Early Genes; Implant; Knowledge; Learning; Link; Medial; Methods; Modernization; Morphology; Motivation; Muscimol; National Institute of Neurological Disorders and Stroke; Nature; Neuronal Plasticity; Neurons; Neurosciences; Nootropic Agents; Pharmacology; Physical environment; Play; Preoptic Areas; Process; Production; Prosencephalon; Regulation; Reporting; Research; Role; Seasonal Variations; Serinus; Sex Differences; Site; Social Behavior; Social Environment; Songbirds; Steroids; Structure; System; Testing; Testosterone; Thinking; Variant; Ventricular; Work; adult neurogenesis; behavioral outcome; behavioral plasticity; brain behavior; brain morphology; design; experimental study; falls; hormone regulation; insight; learned behavior; male; medial preoptic nucleus; neural circuit; neuroblast; neurogenesis; novel; programs; relating to nervous system; reproductive success; resilience; response; sex; social communication; steroid hormone; trait; vocal control; vocal learning; vocalization; x-ray irradiation

Project Summary Basic and clinical research that was initiated in the late 20th century and continues to this day has transformed our thinking about brain resilience. The term brain plasticity is often invoked to describe adaptive changes in the adult brain. This proposed research program concerns the study of neuroplasticity in a seasonal context. This phenomenon involves naturally occurring brain changes that allow an animal to cope with seasonal variation in the physical and social environment to facilitate survival and reproductive success. We study how the steroid hormone testosterone regulates brain changes and the associated changes in behavior in seasonally breeding male and female canaries. These birds possess a well-defined neural circuit, called the song system, which regulates an important learned social behavior, song. Song varies seasonally in that it is more common and more complex in spring when it is produced primarily by males to attract females. Females also produce song but at a lower rate with simpler structure. Key forebrain song nuclei are much larger in volume in the spring in males than in the fall when song is produced less frequently; these song nuclei volumes also are larger in males than in females. Such seasonal changes in brain and behavior may recapitulate behavioral and brain plasticity that occurs during the vocal learning process. Our recent work in canaries has shown that testosterone acts in a pleiotropic manner to regulate multiple aspects of song behavior by having anatomically specific effects in the forebrain song nuclei and in the medial preoptic area, that testosterone can induce male-like changes in neurogenesis and in song behavior in adult female canaries but apparently cannot induce a complete sex reversal, and finally that species variation in perineuronal nets (specialized structures of the extracellular matrix) correlates with species variation in adult vocal plasticity. In this proposal, we capitalize on these findings by investigating the regulation by steroid hormones of brain plasticity and the related song learning and behavior as well as sex differences in their action. The proposal is organized into four aims. In Aim I we ask whether steroid hormone-induced plasticity in the song control nucleus is similar in males and females. Aim II investigates indirect effects of testosterone on song behavior and brain activity related to song by assessing how steroid action in the medial preoptic nucleus indirectly facilitates song-related immediate early gene expression and singing behavior in the song control circuit. Aim III addresses the critical question of the function of adult neurogenesis in songbirds as we will ablate neuroblasts in a site-specific manner with the use of the focused X- ray irradiation method in the ventricular zone in testosterone-treated male and female canaries and assess the morphological and behavioral consequences of these ablations. In Aim IV we will test the hypothesis that perineuronal nets play an important role in limiting brain and behavioral plasticity as it applies to song learning. This research will contribute to the development of more mechanistic insights into brain plasticity as well as help us identify how steroid hormones might serve in a neuroprotective and/or cognitive enhancer-like manner.

项目摘要 基础和临床研究始于20世纪末，一直延续到今天，已经改变了 我们对大脑韧性的思考。术语大脑可塑性经常被用来描述大脑的适应性变化 成人的大脑。这项拟议的研究计划涉及季节性背景下的神经可塑性研究。这 这种现象涉及到自然发生的大脑变化，使动物能够应对季节变化 促进生存和繁殖成功的物质和社会环境。我们研究类固醇是如何 激素睾丸素调节大脑变化和季节性繁殖中相关行为的变化 雄金丝雀和雌性金丝雀。这些鸟拥有一个定义明确的神经回路，称为歌唱系统，它 调节着一种重要的习得社交行为--歌。歌曲因季节而异，因为它更常见，而且 更复杂的是在春天，当它主要由雄性产生以吸引雌性时。女性也会发出歌声 但速度更低，结构更简单。关键的前脑歌声核团在春季的体积要大得多。 雄性比秋天更少发出歌声；雄性的这些歌声核团体积也更大 而不是雌性。大脑和行为的这种季节性变化可能概括了行为和大脑的可塑性 这发生在声乐学习过程中。我们最近在金丝雀上的研究表明，睾丸激素在 一种多效性的方式来调节歌曲行为的多个方面，通过在 在前脑宋核和内侧视前区，睾酮可以在大脑中诱导类似男性的变化 成年雌性金丝雀的神经发生和鸣叫行为，但显然不能诱导完全的性行为 反转，最后是神经周网络(细胞外基质的特殊结构)中的物种变异 与成人发声可塑性的物种变异有关。在这项提案中，我们通过以下方式利用这些发现 类固醇激素对脑可塑性及相关歌曲学习和行为调节的研究 以及他们行动中的性别差异。该提案分为四个目标。在AIM中，我们问是否 类固醇激素诱导的歌曲控制核团的可塑性在男性和女性中是相似的。AIM II调查 通过评估类固醇激素对歌唱行为和大脑活动的间接影响 视前内侧核的活动间接促进了歌曲相关的即刻早期基因的表达 歌曲控制回路中的歌唱行为。目标三解决成人功能的关键问题 鸣禽的神经发生，因为我们将使用聚焦的X-射线以特定部位的方式消融神经母细胞- 雄性和雌性金丝雀经睾酮处理后脑室区域的射线照射方法 这些消融的形态和行为后果。在目标4中，我们将检验假设 周围神经网络在限制大脑和行为可塑性方面发挥着重要作用，因为它应用于歌曲学习。 这项研究将有助于发展对大脑可塑性的更多机械性见解，并有助于 美国确定类固醇激素如何以神经保护和/或认知增强剂的方式发挥作用。