Network anatomy of olfactory processing

描述（由申请人提供）：了解信息如何在神经元回路中处理是神经科学的中心问题，也是了解大脑如何工作的关键。神经元的功能从根本上取决于它在网络中的连接方式。因此，理解网络连接性（电路结构）和细胞功能之间的关系将有助于我们理解神经元和网络如何转换信息以实现感知和行为。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。黑腹果蝇的嗅觉回路是一个很好的模型系统，因为它在一个小体积中包含相对较少的神经元，现有的工具允许遗传靶向标记，我们对这个系统中神经元功能特性的了解正在迅速扩大。我们将利用这些关键优势来了解嗅觉网络组织的基本规则。该提案将首次生成大规模EM数据集，其中可以重建长距离神经元连接，并对应于其体内生理学已知或可以在不同动物中检查的已识别细胞。具体来说，我们将研究的收敛和发散的投射神经元连接到高阶神经元在两个目标区域的proocerebrum，侧角和蘑菇体。我们假设，侧角神经元接受定型和收敛连接从投射神经元的相同类型。有趣的是，侧角的神经元最近与先天嗅觉行为有关。相比之下，我们假设蘑菇体神经元，已知是至关重要的嗅觉学习，有更多的随机和较少的刻板印象与投射神经元的连接。这些都是关于神经元网络的结构和功能的基本问题，这些神经元网络在苍蝇的嗅觉系统中是唯一可接近的。最后，通过了解神经元网络连接的基本原理，我们将准备比较患病和健康的大脑，以评估神经退行性疾病模型中电路结构如何受到影响，从而合理设计治疗策略。

DESCRIPTION (provided by applicant): 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 connectivity 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.