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: 7655207
• 负责人: Gregory F Ball
• 金额: $ 29.87万
• 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 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7655207
• 关键词: Adult; Androgens; Animals; Antisense Oligonucleotides; Area; Aromatase; Behavior; Behavioral; Biological Models; Birds; Brain; Breeding; Bromodeoxyuridine; Catecholamines; Cell Count; Cell Nucleus; Cells; Clinical; Cues; DSP 4; Data; Degenerative Disorder; Denervation; Dopamine-beta-monooxygenase; Dose; Endocrine; Enzymes; Estrogen Receptors; Event; Female; Fiber; Gene Expression Regulation; Genes; Growth; Hormones; Individual; Intervention; Investigation; Lead; Lesion; Measures; Mediating; Methods; Microtubules; Mitotic; Nervous system structure; Neuronal Plasticity; Neurons; Neurophysiology - biologic function; Neurosciences; Neurotoxins; Photoperiod; Photosensitivity; Physiological; Physiological Adaptation; Plasma; Play; Process; Production; Proteins; Regulation; Reproduction; Role; Seasonal Variations; Seasons; Serinus; Songbirds; Sorting - Cell Movement; Steroids; Stimulus; Structure; Telencephalon; Testing; Testosterone; Time; Tyrosine 3-Monooxygenase; Variant; adult neurogenesis; base; brain morphology; brain volume; cell motility; experience; fiber cell; knock-down; male; migration; nerve supply; neural circuit; neurogenesis; neuronal growth; noradrenergic; public health relevance; reproductive; research study; response; social; steroid hormone; steroid hormone receptor; vocalization

DESCRIPTION (provided by applicant): One of the most important paradigm shifts associated with the growth of modern neuroscience in late 20th century is the realization of the extent to which dynamic changes in brain function are the norm rather than the exception. These changes are collectively referred to as examples of "neuroplasticity" and refer to the fact that experiences of various sorts can lead to enduring changes in the structure and functioning of the adult nervous system. Understanding how such brain changes are regulated and what exactly changes is essential for a full elucidation of neural functioning. Such data are also important to provide a scientific underpinning for clinical brain interventions. In many species, the brain changes regularly in response to environmental stimuli such as those that regulate the timing of seasonal reproduction. These changes regulate behavioral and physiological adaptations required for temperate zone species to survive and reproduce successfully in different seasons. Seasonal variation in the brain of songbirds (e.g., canaries Serinus canaria) has emerged as one of the best model systems for the study of naturally occurring hormone-regulated brain plasticity. The volume of brain nuclei associated with the control of vocalizations changes with season in male songbirds. Testosterone (T) promotes the growth of neuronal processes in the spring. Adult neurogenesis occurs in the songbird brain and one way that T promotes increases in brain volume is via neuronal recruitment and survival in these brain areas. Social stimuli, such as the presence of a female, as well as song activity of an individual male can also induce changes in brain morphology independently of testosterone. Ten experiments organized into 5 aims are proposed to study how T and other events that act independently of T can promote this adult neuroplasticity. In aim I studies are proposed to characterize the timing of changes in brain plasticity in relation to changes in endocrine condition associated with changes in seasonal state and to investigate whether there are changes in the brain responsiveness to T action as a function of seasonal reproductive state. In Aim II studies of environmental cues and behavioral events known to facilitate adult neuroplasticity independently of T will be systematically investigated in relation to cellular events associated with variation in song nucleus volume. In particular social cues as well as variation in song production by a male will be manipulated and measures of cell numbers and fibers expressing enzymes related to catecholamine synthesis in the song nuclei will be assessed. In aim III an experiment is proposed to investigate possible male/female differences in the action of T on adult neuroplasticity. In Aim IV the effects of noradrenergic denervation via a specific neurotoxin on T- dependent and independent regulation of brain plasticity will be investigated. We will compare the effects of such a denervation on the ability of T, social cues and singing activity to promote adult seasonal neuroplasticity. Aim V focuses on the regulation of and role played by doublecortin a protein involved in cell migration in adult neuroplasticity. PUBLIC HEALTH RELEVANCE: The elucidation of how morphological and physiological changes in the adult brain are regulated by steroid hormone action and environmental stimuli can provide a scientific underpinning for clinical interventions aimed at relieving behavioral deficits related to brain lesions or degenerative disorders. The studies proposed here concern the regulation of genes related to adult brain change by steroid hormones as well as by social, activity-dependent and environmental stimuli. The genes whose regulation will be studied can influence adult neurogenesis via actions on the processes of cell migration and cell recruitment into neural circuits.

描述(申请人提供)：与20世纪末现代神经科学的发展相关的最重要的范式转变之一是意识到大脑功能的动态变化在多大程度上是常态而不是例外。这些变化统称为“神经可塑性”的例子，指的是各种经历可以导致成人神经系统结构和功能的持久变化。了解这种大脑变化是如何调节的，以及到底是什么变化，对于全面阐明神经功能是至关重要的。这些数据对于为临床脑干预提供科学依据也很重要。在许多物种中，大脑对环境刺激的反应是有规律的，比如那些调节季节性繁殖时间的刺激。这些变化调节了温带物种在不同季节成功生存和繁殖所需的行为和生理适应。鸣禽(如金丝雀)大脑的季节性变化已成为研究自然发生的激素调节的大脑可塑性的最佳模型系统之一。在雄性鸣禽中，与发声控制相关的大脑核团的体积随季节变化。睾酮(T)在春天促进神经元突起的生长。成体神经发生在鸣禽的大脑中，T促进脑体积增加的一种方式是通过这些脑区的神经元招募和存活。社会刺激，如女性的存在，以及男性个体的歌唱活动，也可以诱导大脑形态的变化，而不依赖于睾丸激素。10个实验被组织成5个目标，旨在研究T和其他独立于T的事件如何促进这种成年神经可塑性。本研究的目的是研究大脑可塑性变化的时间与季节性状态变化相关的内分泌状态变化的关系，并探讨大脑对T作用的反应性是否作为季节性生殖状态的函数发生变化。在AIM II中，对环境线索和行为事件的研究将系统地研究与歌唱核体积变化相关的细胞事件，这些环境线索和行为事件有助于独立于T的成人神经可塑性。特别是，将操纵社会暗示以及男性在歌曲产生方面的变化，并将评估歌曲核团中表达与儿茶酚胺合成相关的酶的细胞数量和纤维的测量。在目标III中，提出了一项实验，旨在研究T对成年神经可塑性的作用可能存在的性别差异。在第四个目标中，将研究通过一种特定的神经毒素去甲肾上腺素能神经对T依赖和独立调节大脑可塑性的影响。我们将比较这种去神经对T、社交线索和歌唱活动促进成人季节性神经可塑性的能力的影响。目的研究成年神经可塑性中细胞迁移相关蛋白Doublecortin的调控和作用。公共卫生相关性：阐明成人大脑的形态和生理变化如何受到类固醇激素作用和环境刺激的调节，可以为旨在缓解与大脑损伤或退行性疾病相关的行为缺陷的临床干预提供科学基础。这里提出的研究涉及类固醇激素以及社会、活动依赖和环境刺激对成人大脑变化相关基因的调节。将研究其调控的基因可以通过作用于细胞迁移和细胞重新进入神经回路的过程来影响成年神经发生。