Structural variation in neuronal circuits as a basis for functional and behavioral individuality

项目摘要 我们对神经系统知识的一个基本空白是理解神经系统中的布线和 神经元回路连接性涉及神经计算和行为的可变性。这一差距出现了 因为解剖连接和功能通常是分开研究的。在这里，我们将组建一个团队， 具有互补技能的研究人员来解决这个问题。我们将联合收割机的几种技术开发 在我们的实验室中，包括在行为过程中的体内钙成像，以研究神经元群体的活动， 感知引导的行为和高通量电子显微镜（EM），以提取一个 这种行为的基础网络。为此，我们将使用果蝇作为模型系统 因为它有一个强大的遗传工具包，易于处理的神经元数量，适合大规模的行为， 屏幕，并且是比较全脑连接组学的现实目标。这使得苍蝇成为一个优秀的 模型开发一个全面的方法来表征神经元电路。 我们将应用我们的新方法来研究种群代码，网络连接和结构功能 个体之间的关系是不同的。虽然众所周知，个人，以及男性和女性， 表现出可变的行为，很少有人了解神经元布线和连接的变化如何与 神经计算和最终行为的变化。在我们的第一个目标中，我们将比较人口代码， 布线和多个同基因个体之间的连接，这些个体在视觉引导方法中表现出差异 行为在第二个目标中，我们将应用类似的方法来研究气味偏好的差异 行为我们将测试如何随机大脑不对称，感觉信号的权重，和本地的剧目 interneurons影响个体大脑内的计算。分析结构-功能关系 个人将检查神经元回路精度和可变性之间的权衡，并揭示如何具体 变异塑造信息处理和行为。我们将生成预测神经元功能的模型， 从电路布线和神经元结构的行为。我们的工作将是第一个比较全脑， 多个个体的突触分辨率连接体，以揭示功能网络的基本约束 组织和发现电路可变性如何支持个性。

Project Summary A fundamental gap in our knowledge of the nervous system is understanding how variations in wiring and connectivity of neuronal circuits relate to variability in neural computations and behavior. This gap has arisen because anatomical connectivity and function are typically studied separately. Here, we will assemble a team of researchers with complementary skills to tackle this problem. We will combine several technologies developed in our labs, including in vivo calcium imaging during behavior to study neuronal population activity during perceptually-guided behaviors and high-throughput electron microscopy (EM) to extract the connectivity of an underlying network essential for that behavior. To do so, we will use Drosophila melanogaster as a model system because it has a powerful genetic toolkit, tractable number of neurons, is amenable to large-scale behavioral screens, and is a realistic target for comparative whole-brain connectomics. This makes the fly an excellent model to develop a comprehensive approach to characterize neuronal circuits. We will apply our new approach to investigate how population codes, network connectivity, and structure-function relationships differ between individuals. Although it is well known that individuals, as well as males and females, exhibit variable behaviors, little is understood about how variations in neuronal wiring and connectivity relate to variations in neural computation and ultimately behavior. In our first aim, we will compare population codes, wiring, and connectivity between multiple isogenic individuals that exhibit differences in visually-guided approach behavior. In a second aim, we will apply similar approaches to investigate differences in odor preference behavior. We will test how stochastic brain asymmetry, weighting of sensory signals, and repertoire of local interneurons influence computations within individual brains. Analyzing structure-function relationships across individuals will examine the tradeoff between neuronal circuit precision and variability, and reveal how specific variations shape information processing and behavior. We will generate models predicting neuronal function and behavior from circuit wiring and neuronal structure. Our work will be among the first to compare whole-brain, synaptic-resolution connectomes of multiple individuals to reveal fundamental constraints on functional network organization and discover how circuit variability supports individuality.