Network anatomy of olfactory processing

项目总结/摘要 了解信息是如何在神经元回路中处理的是神经科学的一个中心问题， 理解大脑如何工作的关键。神经元的功能从根本上取决于 连接在其网络中。因此，了解网络连通性与电路之间的关系 结构和细胞功能将帮助我们了解神经元和网络如何将信息转化为 带来感知和行为。大规模电子显微镜的最新进展使我们能够 开始详细绘制神经网络解剖图。果蝇的嗅觉回路是一个 这是一个很好的模型系统，因为它包含了一个相对较少的神经元在一个小的 卷，现有的工具允许遗传靶向标记，我们的知识，功能特性的 这个系统中的神经元正在迅速扩张。我们将利用这些关键优势来理解规则 潜在的嗅觉网络组织。这一提议将首次产生大规模的EM 数据集，其中可以重建长距离神经元连接并与识别的细胞相对应 其体内生理学是已知的或可以在不同的动物中检查。具体来说，我们将研究 投射神经元对高阶神经元的连接性在两个靶区的收敛和发散 前脑、侧角和蘑菇体。我们假设侧角神经元接受 来自同一类型投射神经元的刻板和会聚连接。有趣的是， 侧角最近被认为与先天嗅觉行为有关。相反，我们假设， 蘑菇体神经元，已知对嗅觉学习至关重要， 与投射神经元的连接。这些都是关于结构和功能的基本问题， 在果蝇的嗅觉系统中，神经元网络是唯一可接近的。最后，通过理解 神经网络连接的基本原理，我们将准备比较患病和健康的大脑 评估神经退行性疾病模型中电路结构如何受到影响，以合理设计 治疗策略。

Project Summary/Abstract Understanding how information is processed in neuronal circuits is a central question in neuroscience and key to understanding how the brain works. A neuron's function is fundamentally dependent on how it is connected within its network. Therefore, understanding the relationship between network connectivity - circuit structure - and cellular function will help us to understand how neurons and networks transform information to bring about perception and behavior. Recent advances in large-scale electron microscopy have allowed us to begin detailed mapping of neural network anatomy. The olfactory circuit of Drosophila melanogaster is an excellent model system for this purpose because it contains a relatively small number of neurons in a small volume, existing tools allow genetically-targeted labeling, and our knowledge about functional properties of neurons in this system is rapidly expanding. We will exploit these key advantages to understand the rules underlying olfactory network organization. This proposal would generate for the first time, large-scale EM datasets in which long-range neuronal connectivity can be reconstructed and corresponded to identified cells whose in vivo physiology is known or can be examined in different animals. Specifically, we will examine the convergence and divergence of projection neuron connecitivity to higher-order neurons in two target regions of the protocerebrum, the lateral horn and the mushroom body. We hypothesize that lateral horn neurons receive stereotyped and convergent connectivity from projection neurons of the same type. Interestingly, neurons in the lateral horn have recently been implicated in innate olfactory behaviors. In contrast, we hypothesize that mushroom body neurons, known to be crucial for olfactory learning, have more random and less stereotyped connectivity with projection neurons. These are fundamental questions about the structure and function of neuronal networks that are uniquely approachable in the olfactory system of the fly. Finally, by understanding the basic principles of neuronal network connectivity we will be poised to compare diseased and healthy brains to assess how circuit structure is affected in models of neurodegenerative disorders to rationally design treatment strategies.