Role of the hippocampal GABA system in the development of post-traumatic stress

点击翻译按钮获取中文摘要

Both genetic disposition and child maltreatment and abuse have been identified as majordeterminants in the development of posttraumatic stress disorder and major depression.We have recently developed a novel animal model of anxiety and affective disorders, in which theexposure of juvenile rats to stress induces a predisposition for the development of anxiety ordepressive symptoms following an emotional trauma in adulthood. We propose to use this modelsystem to explore the role of inhibitory GABAergic neurons in emotional stress in adulthood and inthe predisposition to the development of post-traumatic stress and post-traumatic depression.We focus on GABAergic mechanisms as previous work by one of us (OS) has shown that adeficiency in the GABA synthesizing enzyme, GAD65 results in increased fear and anxiety. Inaddition, we have recently shown that fear conditioning or juvenile stress can reduce the expressionof GAD65 in the amygdala. We have formed a team of four research groups with expertise ranging from behavioral analysis, to system analysis, to the molecular level with the aim of:1. Characterizing changes in postsynaptic GABAergic function in the hippocampusfollowing juvenile stress.2. Characterizing changes in properties of defined GABAergic neurons involved ingeneration of rhythmic activities and plasticity in different fields of the hippocampusfollowing stress.3. Developing strategies for intervention in the emergence of stress/depressionThe proposed project puts forward a novel, integrative approach for translational researchaddressing one of the most urgent issues in biological psychiatry today - improving treatment ofstress-related disorders, and in particular of post-traumatic stress disorder. The uniquely integratedteam assembled here ensures original and yet effective progression of the project that will yield avital understanding of the neurobiology of PTSD that is clearly lacking today.