RUI: Mapping physical networks to functional networks in SCN oscillation

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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.