Neurodevelopmental Underpinnings of Rodent Anxiety and Depressive Behavior

啮齿类动物焦虑和抑郁行为的神经发育基础

基本信息

批准号：
8435509
负责人：
Sarah M Clinton
金额：
$ 22.99万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-15 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8435509
关键词：
ARHGEF5 gene Address Adult Adult Children Affective Animal Model Animals Anxiety Anxiety Disorders Autopsy Award Behavior Behavioral Biological Brain Brain region Breeding Caring Cell Count Depressed mood Development Emotional Emotional disorder Endowment Environment Environmental Risk Factor Exhibits Exposure to FGF2 gene Fibroblast Growth Factor Fostering Functional disorder Gene Expression Gene Expression Profile Genetic Goals Growth Growth Factor Hippocampus (Brain)Human Individual Individual Differences Injection of therapeutic agent Intervention Laboratories Life Life Experience Life Stress Maternal Behavior Mental Depression Methods Mood Disorders Morphology Mothers Neonatal Neurobiology Neurosecretory Systems Pathway interactions Patients Pattern Personality Phenotype Play Postpartum Period Predisposition Rattus Research Risk Rodent Role Shapes Stress System Temperament Time United States National Institutes of Health Work depressive symptoms developmental neurobiology improved neural circuit neurobiological mechanism neurochemistry neurodevelopment novel offspring postnatal pup relating to nervous system research study response trait

项目摘要

This proposal for a NIH Pathway to Independence Award (ROO component) aims to elucidate neurodevelopmental underpinnings of emotional dysregulation which may play a role in the onset of anxiety and mood disorders. Innate differences in personality and emotional reactivity strongly shape how individuals respond to stress, and this biological endowment together with early-life experience can powerfully influence neural and emotional development. Understanding the neurobiological mechanisms whereby inborn and environmental factors interact to contribute to the onset of affective dysfunction in the developing brain is crucial for generating improved preventative treatments. Thus, the proposed studies use a novel animal model of depression and anxiety to elucidate the ontogeny of emotional neural circuits to better understand how altered wiring during development may give rise to emotional dysfunction later in life. Preliminary work revealed that anxiety- and depression-prone Low Novelty Reactive (LR) rats exhibit marked differences in the developing hippocampus compared to High Novelty Reactive (HR) animals. The Specific Aims of this project are examining: 1) the ontogeny of hippocampal circuits in baseline LR versus HR animals; 2) how their behavior and underlying neural circuits are modulated by environmental factors such as maternal care; and 3) how early life manipulation of hippocampal circuitry (via exposure to the growth factor FGF2) impacts brain development and later emotional behavior. The overarching goal of the proposed research is to identify neurodevelopmental mechanisms that may underlie key aspects of individual differences in emotionality and susceptibility to depression and anxiety.

NIH独立奖（ROO组成部分）旨在阐明NIH途径的建议情绪失调的神经发育基础可能在焦虑症中发挥作用和情绪障碍。个性和情感反应性的先天差异强烈地塑造了个人的方式应对压力，这种生物学捐赠以及早期生活经验可以强大影响神经和情感发展。了解天生和天生的神经生物学机制环境因素相互作用是为了有助于发育大脑中情感功能障碍的发作是对于改善预防性治疗至关重要。因此，拟议的研究使用一种新型动物抑郁和焦虑的模型，以阐明情绪神经回路的个体发育以更好地理解开发过程中的接线变化可能会导致以后生活中的情绪功能障碍。初步工作揭示了焦虑和抑郁症的低新颖性反应性（LR）大鼠表现出明显的差异与高新颖的反应性（HR）动物相比，发展中的海马。这个特定的目的项目正在研究：1）基线LR与HR动物中海马电路的个体发育； 2）如何它们的行为和潜在的神经回路受到孕产妇护理等环境因素的调节； 3）海马电路的早期寿命操纵如何影响（通过暴露于生长因子FGF2）大脑发展和后来的情感行为。拟议研究的总体目标是确定神经发育机制可能是情感和情感上个体差异的关键方面的基础对抑郁和焦虑的敏感性。