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

基本信息

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
项目类别：
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

项目摘要

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.

总结在任何系统中都缺乏关于发展经历如何持久的信息。然而，大量的经验例子指导着典型的、非典型的、人类和研究动物的治疗性神经发育结果表明经验依赖性可塑性改变行为相关成熟程序的机制为什么我们的神经生物学理解落后于行为学？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尺度：随着每一个相关的经历而迅速发生的每时每刻的变化，考虑到积累的经验以及经验的持续背景，更长的时间范围- 这些依赖于经验的变化与独立的成熟进程没有交叉。措施或方法可以捕捉这些动态，这是一项巨大的挑战，需要采取一项措施。研究模型在斑胸草雀的发展过程中具有牢固的、既定的经验行为联系。在这些鸟类中，鸣禽的鸣叫经历对它们具有相关的、终生的影响。男性和女性的成人社会行为模式，男性，他所唱歌曲的结构整个成年生活，对于雌性来说，她的歌曲和择偶偏好会一生都在一起。歌曲处理需要男性和女性听觉前脑的高阶关联成分一般来说，转录和翻译的表观遗传和分子调控是明显的。神经可塑性的核心，既成熟又依赖于经验，但在任何情况下尚不完全清楚系统这些机制如何协同运作来编码成熟阶段的经验，以便数月和数年之后，它们就会以稳定的行为出现。我们公布的初步数据导致了我们的结果。中心假设，男性和女性青少年听觉的具体机制前脑虽然受到相同广泛的表观遗传和分子调控过程的控制，但它们是不同的。缩小对经验行为联系的观察与调解这些联系的机制之间的差距联系，我们当前有两个目标，1）确定两性的成人行为都受到表观遗传和分子过程是积累和敏锐的青少年歌曲经验的结果，2) 确定细胞结构和功能的特定介质在幼年雄性和我们将通过三个目标来实现这些目标，其中 1) 测试组蛋白 H3 的作用。乙酰化控制青少年歌曲体验对成人行为模式和监管的强度可能协调该联系的转录因子，2）识别表观遗传和分子生物学的“第一波” 对听到的歌曲的反应会引发神经重塑，3) 确定分子影响的程度已知对成人行为所必需的转录和翻译控制因性别而异。