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核心问题，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（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产生感知和行为。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，因为它在小体积中包含相对较少的神经元，现有的工具允许基因靶向标记，我们对该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理解嗅觉网络组织的基本规则。这一提议将首次产生大规模的EM数据集，其中可以重建远距离神经元连接，并对应于已知体内生理学或可以在不同动物中检查的已鉴定细胞。具体来说，我们将研究投射神经元连接到前大脑的两个目标区域，侧角和蘑菇体的高阶神经元的收敛和发散。我们假设侧角神经元从相同类型的投射神经元接收刻板和收敛连接。有趣的是，侧角的神经元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，与投射神经元有更多的随机和更少的刻板连接。这些是关于神经网络的结构和功能的基本问题，在苍蝇的嗅觉系统中是唯一可接近的。最后，通过了解神经网络连接的基本原理，我们将准备好比较患病和健康的大脑，以评估神经退行性疾病模型中的回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.