Neurodevelopmental Underpinnings of Rodent Anxiety and Depressive Behavior

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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.