Linking Juvenile Experiences with Adult Patterns of Behavior

将青少年经历与成人行为模式联系起来

• 批准号: 10620295
• 负责人: SARAH E LONDON
• 金额: $ 41万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10620295
• 关键词: Acceleration; Acetylation; Acute; Address; Adolescent; Adult; Adverse event; Age; Animal Experimentation; Area; Auditory; Behavior; Behavioral; Behavioral Mechanisms; Binding; Biological Assay; Biology; Birds; Brain; Cell physiology; Cellular Structures; ChIP-seq; Chromatin; Data; Development; Dissection; Epigenetic Process; FRAP1 gene; Female; Genomics; Goals; Hearing; Histone Acetylation; Histone H3; Histones; Human; Individual; Lead; Life; Link; Measures; Mediating; Mediator; Methodology; Methods; Methylation; Modeling; Molecular; Neurobiology; Neuronal Plasticity; Nucleic Acid Regulatory Sequences; Outcome; Output; Partner in relationship; Pattern; Phase; Population; Positioning Attribute; Process; Prosencephalon; Proteins; Publishing; RNA; Research; Risk; Role; Sensory; Services; Sex Differences; Signal Transduction; Social Behavior; Songbirds; Structure; System; Testing; Therapeutic; Transcriptional Regulation; Translations; Work; behavioral outcome; design; experience; in vivo; insight; male; neural circuit; neural initiation; neurobiological mechanism; neurodevelopmental effect; preference; programs; remediation; response; sex; transcription factor; tutoring; zebra finch

Summary. There is a dearth of information in any system about how developmental experiences have lasting influence on behavioral patterns. However, the multitude of examples of experiences directing typical, atypical, and therapeutic neurodevelopmental outcomes in humans and research animals indicates that the mechanisms by which experience-dependent plasticity modifies maturational programs in behaviorally-relevant brain circuits have broad implications. Why does our neurobiological understanding lag behind the behavioral evidence? Perhaps it is because linking juvenile experiences with adult behaviors requires a careful tracking of several timescales: from moment-to moment changes that occur rapidly with each relevant experience, to longer timeframes that take into account accumulated experiences, and the sustained backdrop of experience- independent maturational progression with which these experience-dependent changes intersect. No one measure or methodology can capture these dynamics. This is a large challenge, one that necessitates a research model that has strong, established experience-behavior links across development. The zebra finch songbird is such a model. In these birds, juvenile song experience has relevant and life-long consequences on adult patterns of social behavior in both males and females, in males, the structure of the song he sings his entire adult life and in females, her song and mate preferences; mate pairs stay together their entire lives. Song processing requires the higher-order association components of the auditory forebrain in males and females. Generally, it is obvious that epigenetic and molecular regulation of transcription and translation are at the core of neural plasticity, both maturational and experience-dependent, but it is not yet totally clear in any system how these mechanisms operate in concert to encode experiences during maturational stages such that they emerge as stable behaviors months and years later. Our published and preliminary data lead to our central hypothesis, that the specific mechanisms operating within the male and female juvenile auditory forebrain, while controlled by the same broad epigenetic and molecular regulatory processes, are distinct. To reduce the gap between observations of experience-behavior links and the mechanisms that mediate these connections, we have two current goals, 1) establish that adult behavior in both sexes is influenced by epigenetic and molecular processes as a result of accumulated and acute juvenile song experiences, 2) determine the extent to which specific mediators of cell structure and function are unique in juvenile male and female auditory forebrains. We will achieve these goals in three aims, which 1) test the role of histone H3 acetylation in gating the strength of juvenile song experiences on adult patterns of behavior and the regulatory transcription factors that may coordinate that link, 2) identify the “first wave” of epigenetic and molecular responses to hearing song that initiate neural remodeling, and 3) determine the extent to which molecular control of transcription and translation known to be necessary for adult behaviors differs by sex.

概括。关于发展经验如何持久的任何系统中的信息死亡 对行为模式的影响。但是，指导典型，非典型， 人类和研究动物的热神经发育结果表明 与经验依赖的可塑性修饰符成熟程序相关的机制 脑电路具有广泛的影响。为什么我们的神经生物学理解落在行为背后 证据？也许是因为将青少年经历与成人行为联系起来需要仔细跟踪 几个时间表：从每种相关经验迅速发生的瞬间变化，到 考虑到累积的经验以及经验的持续背景 - 这些经验依赖性变化相交的独立成熟进展。没有人 测量或方法可以捕获这些动态。这是一个巨大的挑战，是必要的 在整个开发中具有牢固，建立的经验行为联系的研究模型。斑马很好 鸣禽是这样的模型。在这些鸟类中，少年歌曲体验对 男性和女性的成人社会行为模式，男性，他唱歌的歌曲的结构 整个成年生活和女性，她的歌曲和伴侣的喜好；伴侣一生都在一起。 歌曲处理需要男性听觉前脑的高阶关联组件， 女性。通常，很明显，转录和翻译的表观遗传和分子调节在 神经塑性的核心，无论是成熟还是经验依赖性，但在任何人中都不完全清楚 系统这些机制如何共同运行以在成熟阶段编码体验，以便 几个月后，它们逐渐成为稳定的行为。我们发布的初步数据导致了我们的 中心假设，即在男性和女性少年听觉中运作的特定机制 前脑虽然受相同的广泛表观遗传和分子调节过程的控制，但却是不同的。到 减少经验 - 行为链接的观察与介导这些链接的机制之间的差距 联系，我们有两个目前的目标，1）确定两性的成年行为都受 由于累积和急性少年歌曲体验的结果，表观遗传和分子过程，2） 确定细胞结构和功能的特定介体在少年男性和 女性听觉前脑。我们将在三个目标中实现这些目标，这是1）测试组蛋白H3的作用 乙酰化在成人行为模式和调节性方面的少年歌曲体验的强度 可能协调该链接的转录因子，2）确定表观遗传和分子的“第一波” 对启动神经重塑的听力歌曲的响应，3）确定分子的程度 对成人行为所必需的转录和翻译的控制因性别而异。