Linking Juvenile Experiences with Adult Patterns of Behavior

摘要在任何系统中，都缺乏关于发展经验如何持久的信息。 影响行为模式。然而，大量的经验指导典型的，非典型的， 以及人类和研究动物的治疗性神经发育结果表明， 经验依赖的可塑性修改行为相关的成熟程序的机制 大脑回路有着广泛的含义。为什么我们的神经生物学理解落后于行为学 证据？也许这是因为将青少年的经历与成年人的行为联系起来需要仔细跟踪 几个时间尺度：从每一个相关经验迅速发生的时刻到时刻的变化， 更长的时间框架，考虑到积累的经验，以及持续的经验背景- 独立的成熟的进展，这些经验依赖的变化相交。没有人 衡量标准或方法可以捕捉这些动态。这是一个巨大的挑战，需要 研究模式，具有强大的，建立经验行为的联系，在整个发展。斑胸草雀 鸣禽就是这样一个典范。在这些鸟类中，幼年的鸣叫经历对它们的行为有着相关的和终身的影响。 成年人的社会行为模式在男性和女性，在男性，他唱的歌曲的结构，他的 在雌性中，她的歌曲和配偶偏好;配偶对一生都在一起。 歌曲处理需要男性听觉前脑的高阶关联成分， 女性一般来说，转录和翻译的表观遗传和分子调控是很明显的， 神经可塑性的核心，成熟和经验依赖，但它还没有完全清楚，在任何 系统这些机制如何协同运作，以编码成熟阶段的经验， 它们会在几个月或几年后表现出稳定的行为。我们公布的和初步的数据导致我们 中心假设，即在男性和女性青少年听觉内运作的特定机制， 前脑，虽然由同样广泛的表观遗传和分子调控过程控制，是不同的。到 减少经验-行为联系的观察结果与调节这些联系的机制之间的差距 联系，我们有两个当前的目标，1）建立成年人的行为在两性都受到影响， 表观遗传和分子过程作为积累和急性少年歌曲经验的结果，2） 确定在何种程度上细胞结构和功能的特定介质是独特的青少年男性， 女性听觉前脑我们将通过三个目标来实现这些目标，1）测试组蛋白H3的作用 乙酰化在青少年歌唱经验强度对成年人行为模式的门控中的作用及其调控 可能协调该链接的转录因子，2）识别表观遗传和分子遗传的"第一波"， 对听觉歌曲的反应，启动神经重塑，和3）确定分子 转录和翻译的控制已知是成人行为所必需的，但因性别而异。

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.