Comparative Neuroanatomy at single-neuron resolution

项目总结 尽管单个神经元偶尔会投射到单个下游目标，但更常见的情况是，它们的神经元 轴突侧支并投射到多个不同的解剖区域。神经解剖学的这一特征一直是 100多年来一直受到重视，理论上认为它对协调整个大脑的状态至关重要。尽管如此， 间接预测在当代神经科学中很大程度上被忽视了。这是因为映射 间接预测实际上已经超出了经验研究的范围，特别是在非人类的情况下 在灵长类动物中，单个神经元可以在很大范围内投射。为了克服这些问题，我们的目标是 全面开发基于测序的方法，使我们能够揭示 非人灵长类单个神经元之间的联系--用测序投影的多重分析方法 (MAPseq)。这种方法允许潜在数千个单个神经元的完整侧枝投射 被映射到一只动物身上。迈向我们目标的第一步是验证基于测序的连接 在猕猴身上的方法，这是以前在老鼠身上开发和验证的方法(Aim1)。然后，有一次 经过验证，我们将确定边缘部分单个神经元的局部和远程连接 猕猴的杏仁核系统。我们在这里的主要重点是确定抵押品预测的模式 从杏仁核到额叶皮质(Fc)，因为它们与许多 精神障碍。利用该方法识别脑内单个神经元的多个投射目标 手中的猕猴大脑，然后我们将比较我们在杏仁核中看到的模式与在老鼠身上看到的模式(目标2)。我们 假设通过Fc在非人灵长类、单个杏仁核中的扩展和分化 与老鼠相比，非人类灵长类动物中的神经元将成为更多的侧枝投射。总而言之，当 成功后，我们的方法有可能完全识别非人类单个神经元的投射轮廓。 灵长类动物。这将使人们能够对非人类灵长类动物中存在的神经解剖网络有新的见解， 为研究比较解剖学和辅助解释功能研究提供了一个强大的新工具 它以非人类灵长类动物和小鼠的杏仁核为靶点。

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.