Comparative Neuroanatomy at single-neuron resolution

单神经元分辨率的比较神经解剖学

• 批准号: 10216577
• 负责人: Roger L Clem
• 金额: $ 75.84万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-15 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10216577
• 关键词: Amygdaloid structure; Anatomy; Animal Model; Animals; Area; Axon; Bar Codes; Basic Science; Behavioral; Brain; Cancer Biology; Comparative Anatomy; Data; Development; Disease; Disease model; Distant; Foundations; Functional disorder; Future; Goals; Gold; Hand; Hour; Human; Individual; Injections; Investigation; Knowledge; Label; Limbic System; Link; Macaca; Magnetic Resonance Imaging; Maps; Mediating; Mental disorders; Messenger RNA; Methods; Modeling; Modernization; Monkeys; Multiplexed Analysis of Projections by Sequencing; Mus; Neuroanatomy; Neurons; Neurosciences; Pathway interactions; Pattern; Physiological; Play; Price; Primates; Protocols documentation; RNA Sequences; Resolution; Rest; Rodent; Role; Sensory; Sindbis Virus; Site; Structure-Activity Relationship; Technology; Testing; Time; Tissues; Translational Research; Viral; Virus; base; comparative; frontal lobe; innovation; insight; locus ceruleus structure; nonhuman primate; novel; reconstruction; single cell sequencing; tool; tumor immunology

Project summary Although single neurons occasionally project to a single downstream target, it is more often the case that their axons collateralize and project to multiple distinct anatomical areas. This feature of neuroanatomy has been appreciated for over 100 years and is theorized to be critical to coordinating brain-wide states. Despite this, collateral projections have largely been overlooked in contemporary neuroscience. This is because mapping collateral projections has practically been beyond the reach of empirical investigation, especially in non-human primates where single neurons can project over wide areas. To surmount these issues, our goal here is the comprehensive development of a sequencing-based approach that will allow us to reveal the patterns of connections of single neurons in non-human primates using Multiplexed Analysis of Projections by Sequencing (MAPseq). This approach allows the full collateral projections of potentially thousands of individual neurons to be mapped in a single animal. The first step towards our goal is to validate a sequencing-based connectomic approach in macaque monkeys that has previously been developed and validated in mice (Aim1). Then, once validated we will determine the local and long-range connections of individual neurons in one part of the limbic system in macaques, the amygdala. Our primary focus here is to determine the patterns of collateral projections from amygdala to the frontal cortex (FC) as these have been implicated in the pathophysiology of many psychiatric disorders. With the method for discerning the multiple projection targets of single neurons in the macaque brain in hand we will then compare the patterns that we see in amygdala to those in mice (Aim 2). We hypothesize that through the expansion and differentiation of FC in non-human primates, single amygdala neurons in non-human primates will be many more collateral projections compared to mice. In summary, when successful, our approach has the potential to fully discern the projection profiles of single neurons in non-human primates. This will enable novel insights into the neuroanatomical networks present in non-human primates, provide a powerful new tool for investigating comparative anatomy and aid interpretation of functional studies that target the amygdala in both non-human primates and mice.

项目摘要 虽然单个神经元偶尔会投射到单个下游靶点，但更多情况是它们的神经元投射到下游靶点。 轴突与多个不同的解剖区域平行并投射。神经解剖学的这一特点 100多年来一直受到赞赏，理论上对协调全脑状态至关重要。尽管如此， 在当代神经科学中，侧支投射在很大程度上被忽视了。这是因为映射 抵押预测实际上已经超出了经验调查的范围，特别是在非人类的情况下。 单个神经元可以投射到大范围的灵长类动物。为了克服这些问题，我们的目标是 全面发展一种基于测序的方法，使我们能够揭示 用多重投射分析测序法研究非人灵长类动物单个神经元的连接 （MAPseq）。这种方法允许潜在的数千个个体神经元的完整侧支投射， 在一种动物身上被映射。实现我们目标的第一步是验证基于测序的连接组学 在猕猴中的方法，以前已经开发并在小鼠中验证（Aim1）。然后一旦 我们将确定在边缘系统的一个部分中单个神经元的局部和长程连接 杏仁核系统。我们的主要重点是确定侧支投射的模式 从杏仁核到额叶皮质（FC），因为这些已经涉及许多人的病理生理学。 精神疾病利用神经元多投射靶点的识别方法， 然后，我们将比较我们在杏仁核中看到的模式与小鼠中看到的模式（目的2）。我们 假设通过非人类灵长类FC的扩展和分化，单个杏仁核 与小鼠相比，非人类灵长类动物的神经元将是更多的侧支投射。总之，当 成功的，我们的方法有可能充分辨别非人类单个神经元的投影轮廓 灵长类动物这将使人们对非人类灵长类动物的神经解剖网络有新的认识， 为比较解剖学研究提供了一种强有力的新工具，并有助于解释功能研究 针对非人类灵长类动物和小鼠的杏仁核。

项目成果

Foraging with the frontal cortex: A cross-species evaluation of reward-guided behavior.

• DOI: 10.1038/s41386-021-01140-0
• 发表时间: 2022-01
• 期刊: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
• 作者: Rudebeck PH;Izquierdo A
• 通讯作者: Izquierdo A