Collaborative Research: Higher-order processing in a peripheral neural structure of a nudibranch mollusc

合作研究：裸鳃类软体动物周围神经结构的高阶处理

• 批准号: 2227963
• 负责人: Paul Katz
• 金额: $ 107.38万
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2227963&HistoricalAwards=false
• 关键词: Collaborative; Research; Higher; order; processing

In neuroscience and in biology more broadly, universal principles are determined by comparing a wide variety of different organisms. A tenet of neuroscience is that higher-order computations are performed by neural circuits in the central nervous system (CNS), not the peripheral nervous system (PNS). However, this might not be universally true for all types of animals. This project examines whether olfactory processing circuitry in a mollusc is found in the PNS rather than the CNS, as it is in other animal phyla such as vertebrates and insects. The project uses the nudibranch mollusc, Berghia stephanieae, which is a charismatic lab-grown species that is an inexpensive alternative to many other neuroscience laboratory species, thereby increasing access to research for students. Berghia, like other gastropod molluscs has large, individually identifiable neurons in its CNS. However, like its distant cousin, the octopus, far more small neurons are located in its PNS, which contains peripheral ganglia and sub-epithelial neurons. Anthro¬po¬centricism has biased researchers to believe that the brain is more important than the periphery. However, this might not be true for all types of nervous systems. Determining the extent to which peripheral systems in molluscs perform computations that were thought to be reserved for the brain could transform our view of what actually constitutes a brain.The goal of the project is to elucidate the neural architecture and function of the peripheral rhinophore complex, which consists of the rhinophore, a dorsal cephalic appendage used for distance chemoreception, and the associated rhinophore ganglion. A connectomics and transcriptomics approach will be used to determine whether there are glomeruli in the rhinophore complex that are organized like olfactory glomeruli in the olfactory bulb of vertebrates and the antennal lobe of insects. There are three objectives: 1) A connectome of the rhinophore ganglion will be constructed from volume serial electron microscopic images using machine-learning algorithms to determine the neural circuit motifs that it contains. Customization of machine-learning algorithms to the ultrastructural features of Berghia will facilitate connectomics research in other molluscs. 2) An atlas of neuronal types will be assembled, which will include neurons in the rhinophore complex and neurons that input to it. Neural gene expression, determined from single cell RNA sequencing, will be mapped using in situ hybridization chain reaction (HCR), immunohistochemistry (IHC), and axon tracing. A web portal will provide access to the annotated connectome and neuronal atlas, allowing researchers and students to explore genes, neurons, and neural circuitry in Berghia. 3) The role of the rhinophore complex in navigational behavior will be explored with behavioral assays and selective lesions, taking advantage of Berghia’s regenerative abilities. Laboratory courses developed using Berghia will allow undergraduate students to label and image neurons with HCR and IHC and perform behavioral experiments with automated tracking. This will enable students to make discoveries and test hypotheses regarding neurons and neural circuits in parallel to the discoveries made by laboratory researchers.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

在神经科学和更广泛的生物学中，普遍原理是通过比较各种不同的生物体来确定的，神经科学的一个原则是，高阶计算是由中枢神经系统（CNS）中的神经回路执行的，而不是周围神经系统。 (PNS)。然而，这可能并不适用于所有类型的动物，该项目检查软体动物的嗅觉处理电路是否存在于 PNS 而不是 CNS，就像其他动物门一样。该项目使用裸鳃类软体动物 Berghia stephanieae，这是一种极具魅力的实验室培育物种，是许多其他神经科学实验室物种的廉价替代品，从而增加了学生对 Berghia 的研究机会，就像其他腹足类软体动物一样。它的中枢神经系统中存在大量可单独识别的神经元，然而，与它的远亲章鱼一样，其PNS中也存在更多的小神经元，其中包含外周神经节和神经节。人类中心论使研究人员相信大脑比外周更重要，但对于所有类型的神经系统来说，这可能并不正确。被认为是为大脑保留的神经元可以改变我们对大脑实际构成的看法。该项目的目标是阐明外周犀牛复合体的神经结构和功能，该复合体由犀牛，一种用于远距离化学感受的头侧附属器，以及相关的犀牛神经节，将使用连接组学和转录组学方法来确定犀牛复合体中是否存在像脊椎动物嗅球和触角中的嗅觉肾小球一样组织的肾小球。昆虫的叶有三个目标：1）犀牛神经节的连接组将是使用机器学习算法从体积序列电子显微图像构建以确定其包含的神经回路图案 根据 Berghia 的超微结构特征定制机器学习算法将促进其他软体动物的连接组学研究 2) 神经类型图谱。被组装，其中包括犀牛复合体中的神经元和输入到其中的神经元，通过单细胞 RNA 测序确定神经基因表达，将使用原位杂交链式反应 (HCR) 进行定位。免疫组织化学 (IHC) 和轴突追踪将提供带注释的连接组和神经图谱的访问，使研究人员和学生能够探索 Berghia 的基因、神经元和神经回路。 3) 犀牛复合体在导航行为中的作用。将通过行为分析和选择性损伤进行探索，利用 Berghia 的再生能力，利用 Berghia 开发的实验室课程将允许本科生使用 HCR 和 IHC 标记和成像神经元并执行行为。这将使学生能够与实验室研究人员所反映的发现并行地做出有关神经元和神经回路的发现和测试假设。该奖项是 NSF 的法定使命，并且通过使用基金会的智力价值进行评估，被认为值得支持。以及更广泛的影响审查标准。