Linking Juvenile Experiences with Adult Patterns of Behavior

总结。在任何系统中都缺乏关于发展经验如何持续的信息 对行为模式的影响。然而，指导典型的、非典型的、 在人类和研究动物中的治疗神经发育结果表明 经验依赖性可塑性改变行为相关成熟程序的机制 大脑回路具有广泛的含义。为什么我们对神经生物学的理解落后于行为学 证据呢？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：从瞬间到瞬间随着每一次相关体验而迅速发生的变化，到 考虑到积累的经验和持续的经验背景的更长时间框架- 独立的成熟进程，与这些依赖经验的变化相交。无名之辈 衡量标准或方法可以捕捉到这些动态。这是一个巨大的挑战，需要一个 在整个发展过程中具有强大的、已建立的经验-行为联系的研究模型。斑马雀 Songbird就是这样一个典范。在这些鸟类中，青少年的歌唱经历对 成年人的社会行为模式在男性和女性中，在男性中，他唱的歌的结构 在整个成年生活中，在雌性中，她的歌曲和配偶的喜好；伴侣对在一起度过他们的一生。 歌曲的处理需要男性听觉前脑的高阶联想成分， 女性。一般来说，很明显，表观遗传和分子调控转录和翻译是在 神经可塑性的核心，既有成熟的，也有经验依赖的，但在任何 这些机制如何协同工作以编码成熟阶段的经验，从而 在几个月和几年后，它们会以稳定的行为出现。我们公布的和初步的数据导致了我们的 中心假说，男性和女性青少年听觉中的特定机制 前脑虽然受到同样广泛的表观遗传和分子调控过程的控制，但却是截然不同的。至 减少对经验-行为联系的观察和调节这些联系的机制之间的差距 联系，我们目前有两个目标，1)建立成年人的行为受到 表观遗传和分子过程作为积累和急性青少年歌唱经验的结果，2) 确定细胞结构和功能的特定介质在青少年男性和 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 乙酰化在门控青少年歌唱体验中对成人行为模式的调节作用 可能协调这种联系的转录因子，2)识别表观遗传和分子的“第一波” 对启动神经重塑的听觉歌曲的反应，以及3)决定分子 已知的成人行为所必需的转录和翻译控制因性别而异。

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.