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根本鸿沟是理解大脑中的连线和 神经元回路的连通性与神经计算和行为的可变性有关。这一差距已经出现 因为解剖学的连通性和功能通常是分开研究的。在这里，我们将组建一支 具有互补技能的研究人员来解决这个问题。我们将把开发的几项技术结合起来 在我们的实验室中，包括体内钙成像期间的行为，以研究神经元群体的活动 感知引导行为和高通量电子显微镜(EM)，以提取连接 对该行为至关重要的底层网络。为此，我们将使用黑腹果蝇作为模型系统 因为它有一个强大的遗传工具包，易于处理的神经元数量，是服从大规模的行为 屏幕，是比较全脑连接学的现实目标。这使得苍蝇成为一只优秀的 模型，以开发一种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人口编码、网络连通性和结构功能 人与人之间的关系各不相同。尽管众所周知，个人以及男性和女性， 表现出不同的行为，但对神经元连接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， 在视觉引导的方法中表现出差异的多个等基因个体之间的连接和连接 行为。在第二个目标中，我们将使用类似的方法来研究气味偏好的差异 行为。我们将测试随机的大脑不对称性，感觉信号的权重，以及局部 中间神经元影响个体大脑中的计算。分析结构与功能之间的关系 个人将研究神经元回路精确度和变异性之间的权衡，并揭示其具体程度 变化的形状信息处理和行为。我们将生成预测神经元功能和 从电路布线和神经元结构来看的行为。我们的工作将是第一批比较全脑的工作之一， 多个个体的突触分辨连接揭示对功能网络的基本限制 组织并了解电路变异性如何支持个性。

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.