Characterize the functional connectivity of hippocampal adult neurogenesis during critical period

表征关键期海马成人神经发生的功能连接

• 批准号: 9092230
• 负责人: Xue Han
• 金额: $ 24.65万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9092230
• 关键词: Adult; Age; Antibodies; Area; Behavior; Behavioral; Bilateral; Biological Neural Networks; Bypass; Cell Maturation; Cells; Cognitive; Contralateral; Development; Down-Regulation; Electrophysiology (science); Exhibits; Glutamates; Hippocampus (Brain); Human; Imagery; Interneurons; Label; Membrane; Mental disorders; Microscopy; Neurons; Optics; Pathology; Pattern; Pharmacogenetics; Physiology; Play; Population; Process; Property; Pyramidal Cells; Recruitment Activity; Replacement Therapy; Resolution; Role; Synapses; Synaptic plasticity; Techniques; Time; adult neurogenesis; behavior influence; biophysical properties; cholinergic; critical period; dentate gyrus; experience; flexibility; granule cell; in vivo; insight; interest; nervous system disorder; neural circuit; neurogenesis; optogenetics; public health relevance; young adult

 DESCRIPTION (provided by applicant): Accumulating evidence suggests that neurogenesis continues in the adult mammalian hippocampus including that of humans, and is relevant for many cognitive behaviors. New neurons generated in the dentate gyrus area of the adult hippocampus mature into dentate granule cells and integrate into existing neural circuits. While adult born dentate granule cells (abDGCs) continue their morphological development for an extended period of time, there seems to be a transient maturation period when immature young abDGCs exhibit heightened membrane excitability and elevated synaptic plasticity. Recent studies through pharmacogenetics and optogenetic down regulation of adult neurogenesis have provided important insights on how a small population of abDGCs may exert specific behavioral influence, from spatial pattern separation to cognitive flexibility, and how different ionic currens may contribute to the unique biophysical properties observed during abDGCs critical maturation periods. However, it is largely unclear how adult neurogenesis influences DG neural network in vivo, and how changes in abDGCs' biophysical and synaptic properties during critical maturation period relate to their behavioral impacts. Recently, we developed a robust optogenetic platform capable of transiently silencing a set of age-defined abDGCs to bias behavior and to influence hippocampal neural network dynamics. We here will use this optogenetic platform to further analyze the neural network impacts of age-defined abDGCs on bilateral hippocampus. In addition, we will use the recently invented expansion microscopy technique to perform super-resolution anatomical characterizations of abDGCs' connectivity patterns relevant for their functional impacts. Upon completion of this study, we hope to provide a detailed, time resolved understanding of changes in the neural network connectivity patterns of abDGCs through maturation, and to advance our understanding of the functional significance of adult neurogenesis in physiology and pathology.

 描述（由适用提供）：积累的证据表明，在包括人类的成年哺乳动物海马中，神经发生继续存在，并且与许多认知行为有关。在成年海马成熟的牙科牙齿颗粒细胞中产生的新神经元，并整合到现有的神经元回路中。尽管成年出生的牙齿颗粒细胞（ABDGC）在很长一段时间内继续其形态学发育，但似乎有一个短暂的成熟时期，未成熟的年轻ABDGC暴露了增强的膜令人兴奋和升高的合成可塑性。通过药物遗传学和成年神经发生的光遗传学调节的最新研究为少数ABDGC人群如何发挥特定的行为影响提供了重要的见解，从空间模式分离到认知柔韧性，以及不同的离子货币如何对ABDGC近期观察到的独特的生物物理特性有任何贡献。然而，在很大程度上不清楚成年神经发生如何影响体内DG神经元网络，以及在关键成熟期内ABDGCS的生物物理和突触特性的变化如何与其行为影响有关。最近，我们开发了一个强大的光遗传平台，能够瞬时将一组年龄定义的ABDGC沉默以偏向行为并影响海马神经网络动力学。我们在这里将使用此光遗传平台进一步分析年龄定义的ABDGC对双侧海马的影响。此外，我们将使用最近发明的扩展显微镜技术来执行ABDGCS连接模式与功能影响相关的超分辨率解剖特征。这项研究完成后，我们希望通过成熟来提供对ABDGC神经网络连通性模式的变化的详细，时间解决的理解，并促进我们对成人神经发生在生理学和病理学中的功能意义的理解。