RUI: Mapping physical networks to functional networks in SCN oscillation

RUI：在SCN振荡中将物理网络映射到功能网络

基本信息

批准号：
1749500
负责人：
Rae Silver
金额：
$ 145万
依托单位：
Barnard College
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2024-04-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1749500&HistoricalAwards=false
关键词：
RUI Mapping physical networks functional

项目摘要

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.

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。本项目使用大脑的昼夜节律时钟，下丘脑中的肌核上核，作为解决此问题的模型系统。在大脑时钟中，可以在多个层面上研究单个元素相互作用的方式。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。该项目旨在揭示有关单个神经元如何在大脑时钟产生24小时节奏的网络中如何连接的新信息，以及该主脑时钟如何为身体其余部分提供时机信息。众所周知，每个神经元都有自己的内部时钟，在时间和空间中组织成具有稳定相位关系的不同群集。初步数据表明，大脑时钟包含细胞的“环”。这是令人兴奋的：这是下丘脑核中功能网络形态的第一次演示。从经典上讲，下丘脑被视为松散组织的神经元集合。在其他大脑区域（例如听觉或视觉皮层）中，神经元在特定的三维空间形成中组织，对于信息编码很重要。这项研究的目的是了解界核上的信息编码，以及新发现的环如何有助于大脑时钟的网络和功能。在所有工作中，研究的生物学和数学方面的研究都吸引了对神经科学和应用数学感兴趣的女性本科生。下丘脑的上核核（SCN）是大脑中的大师时钟。该项目的目的是深入了解SCN中的信息编码，并阐明SCN中单元格之间的环形布置如何促进时钟的网络和功能。第一项研究通过使用体内SCN的冠状，矢状和水平切片来建立环的方向。结果有助于发展SCN内相干结构的数学模型的发展。第二项研究涉及使用组织清除方法可视化在SCN切片中观察到的环的结构。第三项研究旨在测试成人和发育过程中以及具有改变昼夜节律性的突变的动物中环的功能。在每个步骤中，环函数的数学模型都是与生物学工作并行开发的，并用于开发有关如何进一步理解环结构的想法。这些研究的结果为SCN组织的先前建立的方面提供了新的分析水平，并扩展了对SCN的广泛认可的核心/壳结构的理解。一个统一的假设是，这个多尺度的组织为昼夜节律振荡系统提供了鲁棒性和韧性，这是通过建模，模拟和野生型SCN的模型，模拟和生物学分析进行检验的假设。该奖项反映了NSF的法定任务，并通过评估智力效果和广泛的范围来进行评估，并通过评估了支持。

项目成果

期刊论文数量（13）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Arginine Vasopressin-Containing Neurons of the Suprachiasmatic Nucleus Project to CSF

视交叉上核中含有精氨酸加压素的神经元投射到脑脊液

DOI：
10.1523/eneuro.0363-20.2021
发表时间：
2021
期刊：
eneuro
影响因子：
3.4
作者：
Taub, Alana;Carbajal, Yvette;Rimu, Kania;Holt, Rebecca;Yao, Yifan;Hernandez, Amanda L.;LeSauter, Joseph;Silver, Rae
通讯作者：
Silver, Rae

Elevated zinc transporter ZnT3 in the dentate gyrus of mast cell‐deficient mice