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空间精确的方式进行处理。然而，嗅觉子系统的组织背后的原理还没有被很好地理解。这项研究计划的目的是调查鳗的外周嗅器官和嗅球的细分部分的气味敏感性、生化特征和神经连接。七鳃鳗是一种基本脊椎动物，在5亿多年前从主要脊椎动物进化路线中分离出来。硬骨鱼闻到成百上千种气味，哺乳动物对成千种气味分子做出反应，七鳃鳗则拥有几十种气味的嗅觉能力。然而，嗅觉是一种关键的感觉方式，因为信息素在产卵、迁徙和繁殖行为期间指导七鳃鳗。这些特性使得七鳗鱼可以被用作研究脊椎动物嗅觉的简化论模型。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，但投射到该球区域的嗅觉神经元群体尚不清楚。我们将利用神经束追踪来寻找这些嗅觉神经元的外周位置和细胞形态，并通过光学成像和电生理学来研究这些嗅觉神经元的信号转导途径。束追踪将被用来研究球外侧投射神经元的树突，以检查传递氨基酸嗅觉的神经元的会聚程度。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。我们将调查是否有专门负责与迁徙和繁殖相关的特定信息素的特定区域。束追踪将被用来识别信息素感觉神经元的外围位置、中央投射和相应的球部投射神经元。在衍生脊椎动物中，嗅觉感觉神经元亚型表达特定的传导通道，这些通道与信号转导通路合作。最近对海鳗基因组的注释为研究不同种群的海鳗嗅觉神经元表达的特定传导通道提供了机会。这一信息对于在一般脊椎动物模型中定义七鳃鳗嗅觉子系统非常重要。这项研究计划探索脊椎动物神经系统进化中的共性和差异性。它意义重大，因为它将有助于了解嗅觉感觉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七鳃鳗以及欧洲和北美西海岸濒危种群的野生动物管理。

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.