Activation and connectivity in the olfactory system of a basal vertebrate

在许多脊椎动物中，嗅觉感觉输入发生在鼻腔内的多个位置，气味信息在嗅球中以精确的空间方式处理。然而，嗅觉子系统组织背后的基本原理还没有得到很好的理解。本研究项目的目的是研究七鳃鳗的气味敏感性、生化特征和神经连通性。七鳃鳗是一种基础脊椎动物，在5亿多年前从主要脊椎动物进化路线中分离出来。硬骨鱼可以闻到数百种气味，哺乳动物可以对数千种气味分子做出反应，而七鳃鳗的嗅觉能力只有几十种。然而，嗅觉是一种关键的感觉方式，因为信息素直接指导七鳃鳗产卵迁徙和繁殖行为。这些特征使七鳃鳗可以作为研究脊椎动物嗅觉的简化模型。我们最近利用体外七鳃鳗鼻脑准备的电生理学来表征嗅球的气味激活图。外侧区域对氨基酸有反应，但投射到这个球区的嗅觉感觉神经元数量是未知的。我们将利用神经束追踪来发现这些嗅觉感觉神经元的外周位置和细胞形态；我们将通过光学成像和电生理学研究这些嗅感觉神经元的信号转导途径。束示踪将用于研究外侧球投射神经元的树突乔木，以检查传递氨基酸嗅觉的神经元的收敛程度。虽然嗅球的外侧区域受到氨基酸的刺激，但对信息素的空间反应图却不太清楚。我们将研究是否有特定的区域专门用于与迁移和繁殖有关的特定信息素。束追踪将用于识别信息素感知神经元，中央投射和相应的球投射神经元的外围位置。在衍生的脊椎动物中，嗅觉感觉神经元亚型表达与信号转导途径合作的特定传导通道。最近对海七鳃鳗基因组的注释为研究不同种群的海七鳃鳗嗅觉感觉神经元表达的特定电导通道的表达提供了机会。这些信息对于根据一般脊椎动物模型定义七鳃鳗的嗅觉子系统是重要的。本研究项目探讨脊椎动物神经系统进化的共性与差异。这项研究意义重大，因为它将有助于了解嗅觉感官输入的方式和原因，以及随后的中枢连接。在更广泛的范围内，这项研究将有助于了解大脑的进化，以及脊椎动物的大脑如何处理来自各种化学刺激的信息。这项研究的翻译将直接有利于五大湖入侵的海洋七鳃鳗的野生动物管理，以及欧洲和北美西海岸濒临灭绝的种群。

In many vertebrates, olfactory sensory input takes place in more than one location within the nasal cavity, and odour information is processed in a spatially precise manner in the olfactory bulb. However, the rationale behind the organization of the olfactory subsystems is not well understood. The objective of this research program is to investigate the odor sensitivity, biochemical profile and neural connectivity in subdivisions of the peripheral olfactory organ and the olfactory bulb in the lamprey, a basal vertebrate that diverged from the main vertebrate line of evolution over 500 million years ago. While teleost fish smell hundreds of odours, and mammals respond to thousands of odorous molecules, the lamprey has an olfactory repertoire of a few dozen odourants. Yet olfaction is a key sensory modality, as pheromones direct lampreys during spawning migration and reproductive behaviour. These characteristics enable the lamprey to be utilized as a reductionist model for investigating vertebrate olfaction. We have recently utilized electrophysiology of an in vitro lamprey nose-brain prep to characterize the odour activation map of the olfactory bulb. The lateral region responds to amino acids, yet the olfactory sensory neuron population that projects into this bulbar region is unknown. We will utilize neuronal tract tracing to find the peripheral location and the cell morphology of these olfactory sensory neurons; and we will investigate the signal transduction pathways of these olfactory sensory neurons through optical imaging and electrophysiology. Tract tracing will be used to investigate the dendritic arbors of lateral bulbar projection neurons, to examine the degree of convergence of the neurons that convey amino acid olfaction. While the lateral region of the olfactory bulb is stimulated by amino acids, there is a less clear picture of the spatial response map to pheromones. We will investigate if there are specific regions devoted to specific pheromones associated with migration and reproduction. Tract tracing will be used to identify the peripheral location of the pheromone sensing neurons, the central projections and the corresponding bulbar projection neurons. In derived vertebrates, olfactory sensory neuronal subtypes express specific conductance channels that are partnered with signal transduction pathways. The recent annotation of the sea lamprey genome opens up opportunities for investigating the expression of specific conductance channels expressed by the different populations of sea lamprey olfactory sensory neurons. This information is important for defining the lamprey olfactory subsystems in terms of the general vertebrate model. This research program probes for commonality and divergence in the evolution of the vertebrate nervous system. It is significant because it will contribute knowledge of the how and why of olfactory sensory input and the ensuing central connections. On a broader scale, this research will contribute to knowledge regarding the evolution of the brain and how the vertebrate brain handles information from diverse chemical stimuli. Translation of this research will directly benefit wildlife management of the invasive sea lamprey in the Great Lakes, and endangered populations in Europe and the North American west coast.