Role of dentate granule cell birth date in determining stress-related function

齿状颗粒细胞出生日期在确定应激相关功能中的作用

• 批准号: 9396465
• 负责人: Mary Youssef
• 金额: $ 3.14万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9396465
• 关键词: Adolescent; Adult; Anatomy; Animal Model; Animals; Anxiety; Arousal; Behavior; Behavioral; Birth; Brain; Brain region; Cell physiology; Cells; Chronic stress; Corticosterone; Cytoplasmic Granules; Data; Date of birth; Desire for food; Development; Embryo; Emotions; Goals; Hippocampus (Brain); Hormonal; Hormone Receptor; Human; Label; Lead; Learning; Life; Measures; Memory; Mental Depression; Mental disorders; Mus; Neurons; Pathway interactions; Performance; Physiologic pulse; Physiological; Play; Population; Regulation; Research; Role; Schizophrenia; Specific qualifier value; Stereotyping; Stress; Structure; System; Techniques; Therapeutic; Time; acute stress; anxious; anxious behavior; base; behavioral response; biological adaptation to stress; cohort; density; dentate gyrus; experience; granule cell; hormone regulation; mature animal; novel; optogenetics; postnatal; programs; response; stressor; therapeutic target

PROJECT SUMMARY The stress response consists of stereotyped physiological and behavioral programs that promote survival or enhanced performance during threatening or challenging situations. Stress is beneficial because it allows for a heightened response to the stressor; however, excessive stress is detrimental and can lead to or exacerbate psychiatric illnesses, such as anxiety, depression and schizophrenia. It is important to understand how the brain reacts to stress and regulates the stress response so that these pathways can be therapeutically targeted. The hippocampus is a brain structure that is known to be involved in learning and memory, but it also plays a role in regulation of stress and emotion, and is altered in these stress-related psychiatric illnesses in both humans and animal models. One component of the hippocampus that is sensitive to stress is the dentate gyrus (DG). The DG contains the highest density of stress hormone receptors in the hippocampal region and, moreover, in the entire brain. Additionally, the DG undergoes anatomical and functional changes in response to stress. The DG has been shown to be activated by stress and to regulate the stress response, but the mechanisms by which it does so are unknown. My project seeks to identify the neuronal populations in the DG that perform these functions. The principal cells of the dentate gyrus are granule cells, which reside in a distinct granule cell layer. These DG granule cells are activated by many experiences, including exploration, novelty, stress, and arousal. To understand how the dentate reacts to stress, I will characterize the DG neuronal populations activated by several types of stress. Additionally, I will use optogenetics to activate populations of DG granule cells to elucidate their effect on the hormonal and behavioral response to stress. The hippocampus is altered in many psychiatric illnesses in which stress plays a causal role. Understanding the hippocampal cells and circuits involved in regulation of stress may lead to the identification of potential cellular or circuit-based targets that can be therapeutically manipulated to alter stress regulation or to decrease the negative effects of stress on the brain, and thus, the contribution of stress to mental illness.

项目摘要 应激反应包括促进生存或减轻痛苦的刻板的生理和行为程序。 在威胁或挑战性情况下提高性能。压力是有益的，因为它允许 对压力源的反应增强;然而，过度的压力是有害的，可能导致或加剧 精神疾病，如焦虑症、抑郁症和精神分裂症。重要的是要了解 大脑对压力做出反应并调节压力反应，以便这些途径可以治疗 针对性地 海马体是一种已知与学习和记忆有关的大脑结构，但它也起着重要的作用。 在调节压力和情绪中的作用，并且在这些与压力相关的精神疾病中， 人类和动物模型。海马体中对压力敏感的一个组成部分是齿状回 （DG）。DG在海马区含有最高密度的应激激素受体， 而且是在整个大脑中。此外，DG经历解剖和功能变化， 压力DG被应激激活并调节应激反应，但DG在应激反应中起重要作用。 其机制尚不清楚。我的项目旨在确定DG中的神经元群体 执行这些功能的。 齿状回的主要细胞是颗粒细胞，它们位于不同的颗粒细胞层中。这些DG 颗粒细胞被许多经历激活，包括探索、新奇、压力和觉醒。到 了解齿状回如何对压力作出反应，我将描述DG神经元群被激活的特征。 几种类型的压力。此外，我将使用光遗传学来激活DG颗粒细胞群， 阐明它们对荷尔蒙和行为应激反应的影响。海马体在很多情况下 精神疾病中压力起着因果作用。了解海马细胞和回路 参与应激调节的神经元可能导致识别潜在的基于细胞或电路的靶点， 可以在治疗上被操纵以改变应激调节或减少应激对 大脑，因此，压力对精神疾病的贡献。