Neurodevelopmental Underpinnings of Rodent Anxiety and Depressive Behavior

这项关于美国国立卫生研究院独立途径奖(Roo部分)的提议旨在阐明 情绪失调的神经发育基础，这可能在焦虑的发生中起作用 和情绪障碍。性格和情绪反应的先天差异强烈地塑造了个人 对压力做出反应，这种生物天赋和早期生活经历可以有力地影响 神经和情感的发展。了解先天和后天的神经生物学机制 环境因素相互作用导致大脑发育中情感功能障碍的发生 对于产生改进的预防性治疗至关重要。因此，拟议的研究使用了一种新的动物 用抑郁和焦虑模型来阐明情绪神经回路的个体发生，以更好地理解 发育过程中的线路改变可能会在以后的生活中导致情绪障碍。前期工作 研究表明，易焦虑和易抑郁的低新奇反应(LR)大鼠在 与高新颖性反应(HR)动物相比，发育中的海马体。这样做的具体目的是 项目正在研究：1)基线LR和HR动物的海马环路的个体发育；2)如何 他们的行为和潜在的神经回路受到环境因素的调节，如产妇护理； 3)早期对海马体回路的操纵(通过暴露于生长因子FGF2)如何影响 大脑发育和后来的情绪行为。拟议研究的首要目标是确定 神经发育机制可能是个体情绪和情感差异的关键方面 易患抑郁症和焦虑症。

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.