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 尽管单个神经元偶尔会投射到一个下游目标，但他们的经常是他们的 轴突抵押并投射到多个不同的解剖区域。神经解剖学的这一特征已经 赞赏已有100多年的历史，理论上对于协调整个大脑状态至关重要。尽管如此， 在当代神经科学中，抵押预测在很大程度上被忽略了。这是因为映射 附带预测实际上已经超出了实证研究的范围，尤其是在非人类 单个神经元可以在大区域投射的灵长类动物。为了克服这些问题，我们的目标是 基于测序的方法的全面发展，该方法将使我们能够揭示 通过对投影的多路复用分析，通过测序对非人类灵长类动物中的单个神经元的连接 （MAPSEQ）。这种方法允许可能成千上万个单个神经元的全部附带预测 被映射在单个动物中。迈向我们目标的第一步是验证基于测序的连接组 以前在小鼠中已经开发和验证的猕猴的方法（AIM1）。然后，一次 经过验证，我们将确定边缘一部分中单个神经元的局部和长期连接 猕猴的系统，杏仁核。我们这里的主要重点是确定附带预测的模式 从杏仁核到额叶皮层（FC），因为这些与许多人的病理生理有关 精神疾病。用辨别单个神经元的多个投影靶标的方法 然后，猕猴的大脑将比较杏仁核中看到的模式与小鼠中的模式（AIM 2）。我们 假设通过非人类灵长类动物的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抵押预测。总而言之，什么时候 成功，我们的方法有可能完全辨别非人类单个神经元的投影谱 灵长类动物。这将使对非人类灵长类动物中存在的神经解剖网络的新见解， 提供了一个有力的新工具来研究比较解剖学和功能研究的帮助解释 该靶向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