Neurodevelopmental Underpinnings of Rodent Anxiety and Depressive Behavior

NIH独立之路奖（ROO部分）的提案旨在阐明 情绪失调的神经发育基础可能在焦虑发作中起作用 和情绪障碍性格和情绪反应的先天差异强烈地塑造了个体 对压力作出反应，这种生物禀赋加上早期生活经验可以有力地影响 神经和情感发育了解先天和后天的神经生物学机制， 环境因素相互作用，导致发育中的大脑出现情感功能障碍， 这对于改进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， 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 在发育过程中改变的神经线路如何在以后的生活中引起情感功能障碍。前期工作 揭示了焦虑和抑郁倾向的低新奇反应（LR）大鼠在以下方面表现出显著差异： 与高新奇反应性（HR）动物相比，发育中的海马体。具体目标是 项目正在研究：1）基线LR与HR动物海马回路的个体发育; 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，如母亲的照顾; 以及3）海马电路的早期生活操纵（通过暴露于生长因子FGF 2）如何影响 大脑发育和后来的情感行为。拟议研究的总体目标是确定 神经发育机制，可能是情绪个体差异的关键方面， 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.