RUI: Mapping physical networks to functional networks in SCN oscillation

神经科学的一个广泛目标是了解大脑的结构如何产生其功能。目前的项目使用大脑的主生物钟，下丘脑的视交叉上核，作为一个模型系统来解决这个问题。在大脑时钟中，单个元素相互作用的方式可以在多个层次上进行研究;例如，时钟基因，时钟神经元，整个大脑时钟，或动物的行为和生理学。该项目旨在揭示关于单个神经元如何连接在一个网络中的新信息，该网络在大脑时钟中产生24小时的节奏，以及这个主大脑时钟如何为身体的其他部分提供计时信息。我们已经知道，每个神经元都有自己的内部时钟，它们在时间和空间上被组织成不同的簇，彼此之间具有稳定的相位关系。初步数据表明，大脑时钟包含相位一致，高度组织化的细胞“环”。这是令人兴奋的：这是下丘脑核团内功能网络拓扑学的首次展示。传统上，下丘脑被视为神经元的松散组织集合。在其他大脑区域，如听觉或视觉皮层，神经元以特定的三维空间结构组织起来，这对信息编码很重要。这项研究的目的是了解视交叉上核的信息编码，以及新发现的环如何有助于大脑时钟的网络和功能。在所有的工作中，研究的生物学和数学方面的研究吸引了对神经科学和应用数学感兴趣的女大学生，下丘脑的视交叉上核是大脑中的主时钟。 这个项目的目标是深入了解SCN中的信息编码，并阐明SCN中细胞之间的环状排列如何有助于时钟的网络和功能。第一项研究通过使用体内SCN的冠状、矢状和水平切片来确定环的方向。这些结果有助于发展描述SCN内相干结构的数学模型。第二项研究涉及使用组织清除方法来可视化在SCN切片中观察到的环的结构。第三项研究用于测试成年人和发育期间以及具有改变昼夜节律的突变的动物中的环的功能。在每一步中，环功能的数学模型正在与生物学工作并行开发，并用于开发如何进一步理解环结构的想法。这些研究的结果提供了一个新的水平的分析，以前建立的方面的SCN组织和扩展的理解广泛接受的核/壳结构的SCN。一个统一的假设是，这种多尺度组织提供了鲁棒性和弹性的昼夜振荡系统，一个假设通过建模，模拟和突变和野生型SCN的生物学分析在这里测试。这个奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

A broad goal of Neuroscience is to understand how the structure of the brain gives rise to its functions. The present project uses the brain's master circadian clock, the suprachiasmatic nucleus in the hypothalamus, as a model system to tackle this problem. In the brain clock, the way individual elements interact can be studied at multiple levels; for example, clock genes, clock neurons, the brain clock as a whole, or the behavior and physiology of the animal. The project aims to reveal new information about how individual neurons are connected in a network that produces a 24-hour rhythm in the brain clock, and how this master brain clock provides timing information to the rest of the body. It already is known that individual neurons, each with internal clocks of their own, are organized in time and space into distinct clusters bearing stable phase relationships to each other. Preliminary data indicate that the brain clock contains phase-coherent, and highly organized, "rings" of cells. This is exciting: it is the first demonstration of functional network topography within a hypothalamic nucleus. Classically, the hypothalamus is viewed as loosely organized collections of neurons. In other brain regions, such as the auditory or the visual cortex, neurons are organized in specific 3-dimensional spatial formations that are important for information coding. The goal of this study is to understand information coding in the suprachiasmatic nucleus, and how the newly discovered rings contribute to the brain clock's network and function. In all the work, research in both the biological and mathematical aspects of the studies engages women undergraduate students interested in Neuroscience and in Applied Mathematics.The suprachiasmatic nucleus (SCN) of the hypothalamus is the master clock in the brain. The goal of this project is to gain insight into information coding in the SCN and to elucidate how ring-like arrangements among cells in the SCN contribute to the clock's network and function. The first study establishes the orientation of the rings by using coronal, sagittal, and horizontal slices of the SCN in vivo. The results contribute to the development of mathematical models that characterize coherent structures within the SCN. The second study involves use of tissue clearing methods to visualize the structures of the rings observed in SCN slices. The third study serves to test the function of the rings both in adults and during development and in animals with mutations that alter circadian rhythmicity. At each step, mathematical models of ring functions are being developed in parallel with the biological work, and used to develop ideas on how to further understanding of the ring structures. The results from these studies provide a new level of analysis to previously established aspects of SCN organization and extend the understanding of the widely-accepted core/shell structure of the SCN. A unifying hypothesis is that this multi-scale organization provides robustness and resilience to the circadian oscillatory system, a hypothesis tested here via modeling, simulation, and biological analyses of mutant and wild type SCN.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.