To explore the development and function of clonally-related adult-born dentate gr

探讨克隆相关的成年齿状细胞的发育和功能

• 批准号: 8772093
• 负责人: Shaoyu Ge
• 金额: $ 23.7万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-15 至 2016-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8772093
• 关键词: Adult; Affect; Age; Animals; Behavior; Behavioral; Birth; Brain; Brain Diseases; Cells; Collaborations; Coupling; Cytoplasmic Granules; Date of birth; Development; Electrophysiology (science); Etiology; FOS gene; Failure; Functional disorder; Gap Junctions; Generations; Genetic; Goals; Hippocampus (Brain); Image; Infusion procedures; Label; Laboratories; Light; Memory; Mental disorders; Methods; Microscopy; Monitor; Neuroglia; Neurons; Newborn Infant; Pattern; Pilot Projects; Play; Pluripotent Stem Cells; Population; Property; Radial; Recruitment Activity; Role; Sister; Source; Staging; Stem cells; Synapses; Testing; Time; Viral; Virus; Visual Cortex; Whole-Cell Recordings; aged; aging brain; base; conditioned fear; daughter cell; dentate gyrus; granule cell; information processing; insight; mental age; nerve stem cell; neural circuit; newborn neuron; optogenetics; patch clamp; public health relevance; tool; two-photon

DESCRIPTION (provided by applicant): The dentate gyrus of adult hippocampus continuously generates new granule cells. New granule cells integrate into the existing neural circuits and regulate hippocampal behaviors. In the aged animals, there is not only a substantial decrease in the generation of newborn granule cells but also increasing failure in circuit integration of these new neurons. This raises the importance of understanding the strategy for circuit integration of new neurons in the adult brain, which remains largely unknown. In one of our recent studies in collaboration with Dr. Dan's group, we found that clonally-related sister neurons in the developing cortex are initially synchronized. This suggests that new neurons may share similar properties during integration, and are co- activation during hippocampal function. This motivates us to establish a method to label and manipulate clonally-related newborn granule cells and study their neural circuit integration and activation. As an exploratory study, we will first characterize the development of clonally-related adult-born granule cells. We will perform dual patch clamp whole cell recording of clonally-related granule cells to test their neuronal and synaptic properties during development. Secondly, we will test whether clonally-related adult-born granule cells are preferentially co-activated during 2+ hippocampal activities. To achieve this goal, we will perform Ca and c-fos imaging to study the activation of clonally-related granule cells after they are fully integrated. Importantly, we will test whether the initial synchronizatio of clonally-related adult-born granule cells is required for their development and function. Additionally, using optogenetic method, we will test whether clonally-related new neurons are differentially activated by different laminar activation. Our finding will delineate whether clonaly-related newborn granule cells share a similar developmental track and preferentially recruited during hippocampal activities. We will also test whether the initial gap junction coupling is necessary to normal development and function of clonally-related newborn neurons. These studies will provide some basis for studying the generation and development of new neurons in the aged brain.

描述（申请人提供）：成年海马齿状回不断产生新的颗粒细胞。新的颗粒细胞整合到现有的神经回路中并调节海马行为。在老年动物中，不仅新生颗粒细胞的产生大量减少，而且这些颗粒细胞的电路整合也越来越失败。 新的神经元这提高了理解成人大脑中新神经元电路整合策略的重要性，这在很大程度上仍然是未知的。在我们最近与Dan博士的团队合作的一项研究中，我们发现发育中的皮层中与克隆相关的姐妹神经元最初是同步的。这表明新的神经元在整合过程中可能具有相似的特性，并且在海马功能期间是共激活的。这促使我们建立一种方法来标记和操纵克隆相关的新生颗粒细胞，并研究其神经回路的整合和激活。作为一项探索性研究，我们将首先描述克隆相关的成人出生颗粒细胞的发育特征。我们将进行双膜片钳全细胞记录克隆相关的颗粒细胞，以测试他们的神经元和突触特性在发展过程中。其次，我们将测试克隆相关的成年出生的颗粒细胞是否优先共激活2+海马活动。为了实现这一目标，我们将进行Ca和c-fos成像，以研究克隆相关颗粒的激活 细胞完全整合后。重要的是，我们将测试克隆相关的成人出生颗粒细胞的初始同步化是否是其发育和功能所必需的。此外，我们将使用光遗传学方法测试克隆相关的新神经元是否被不同的层激活差异激活。我们的发现将阐明克隆相关的新生颗粒细胞是否有相似的发育轨迹，并优先在海马活动期间招募。我们还将测试初始间隙连接偶联是否是克隆相关新生神经元正常发育和功能所必需的。这些研究将为研究老年脑内新生神经元的产生和发育提供一定的依据。