Neural and Molecular Basis of Individual Differences in Brain Function and Behavior

项目摘要 神经科学的一个基本目标是确定不同的大脑区域如何影响行为（即， 结构-功能关系）。虽然在发现区域功能方面取得了重大进展 我们对个体之间的结构-功能关系的差异知之甚少， 个体最近的证据表明，在大脑活动中有许多这样的个体差异， 遗传和性别等因素对大脑活动模式有着巨大的影响。但是这些的分子基础 差异及其对行为的影响尚不清楚。为了开始探索这个新领域，我们将（1） 识别与行为的关系受遗传和性别影响的大脑区域，以及（2）识别 基因和性别对大脑功能和行为影响的神经递质和受体。我们 将通过测量探索性行为和长期行为背后的全脑活动模式来做到这一点。 成年斑马鱼的记忆回忆斑马鱼是一种遗传学上易于控制的动物模型，具有以下几个特征 这使它们成为目前研究的理想对象：一个小而简单的形态，一个复杂的行为， 以及基因操作的简易性。作为脊椎动物，斑马鱼与哺乳动物保持高度相似性， 遗传学和神经系统组织。鉴于许多精神健康障碍表现为 神经活动模式，了解生物学中的个体差异如何影响大脑功能， 行为将为开发治疗大脑局部疾病的精确方法提供信息。

PROJECT SUMMARY A fundamental goal of neuroscience is to determine how different brain regions contribute to behavior (i.e. structure-function relationships). Although significant progress has been made in discovering regional functions that are common across individuals, we know little about how structure-function relationships differ between individuals. Recent evidence suggests that there are many such individual differences in brain activity, with factors like genetics and sex have outsize influence on patterns of brain activity. But the molecular basis of these differences, and their consequences for behavior, are unknown. To begin exploring this new territory, we will (1) identify brain regions whose relationship to behavior is influenced by genetics and sex, and (2) identify neurotransmitters and receptors that underlie the influence of genes and sex on brain function and behavior. We will do this by measuring patterns of whole-brain activity that underlie exploratory behavior and long-term memory recall in adult zebrafish. Zebrafish are a genetically tractable animal model with several characteristics that make them ideal for the present research: a small and simple morphology, a sophisticated behavioral repertoire, and ease of genetic manipulation. As vertebrates, zebrafish retain a high similarity to mammals in genetics and nervous system organization. Given that many mental health disorders manifest as alterations in patterns of neural activity, understanding how individual differences in biology influence brain function and behavior will inform the development of precision approaches for the treatment of disorders localized to the brain.