Neuroplasticity of Social Learning

描述（由申请人提供）：创伤事件和慢性应激与应激相关的精神病理学的发展有关。大多数压力相关疾病的动物模型使用严格控制的人工压力源，将这些压力源扩展到更自然的相关压力源是至关重要的。社会压力是一种更自然的应激源，可以抑制低社会地位或长期暴露于社会压力的动物的生殖功能（例如缺乏求偶行为，性腺功能延迟或青春期延迟）。这些研究着眼于神经营养因子在社会地位中的作用，以及短暂的互动如何导致行为的长期变化。他们还研究了慢性社会压力对神经的影响。神经营养因子在不同的病理学中改变了表达，例如癫痫、阿尔茨海默病和帕金森病以及抑郁症。特别是在其与抑郁症的形式，社交失败可能提供洞察这些神经营养因子水平与抑郁症相关的机制。所获得的结果将提供一个基础，开发一个综合模型，可以应用于跨类群。这个建议的基本目标是设计和实施实验，这将有助于我作为一个发展中的分子神经内分泌学家的培训，并阐明社会地位行为中社会介导的修改的机制。本研究的总体目标是：1）描述神经营养因子与支配地位和从属地位的关系; 2）检验神经营养因子在社会地位的获得和维持及其相关行为中的作用。具体来说，我提出了两个相互关联的研究：1）状态依赖性差异的攻击，顺从行为，血浆皮质酮浓度，和神经营养蛋白的大脑mRNA表达和这些因素的关系将被调查，2）直接的实验操作将评估的作用，神经营养蛋白的收购，巩固和维护的社会地位及其相关行为。这些研究将有助于理解社会压力可以引起大脑持续变化的基本过程，例如在创伤后应激障碍和其他心理健康状况的患者中看到的，这些患者因社会压力而加剧或因成功的社会互动而得到帮助。

DESCRIPTION (provided by applicant): Traumatic events and chronic stress have been implicated in the development of stress-related psychopathologies. Most animal models of stress-related disorders use tightly controlled, but artificial stressors, and it is critical to extend these to more natural relevant stressors. Social stress is a more natural stressor and can suppress reproductive function (e.g. lack of courtship behavior, delayed gonadal function, or delayed onset of puberty) in animals of low social status or those exposed to chronic social stress. These studies look at the role of neurotrophins in social status and how a brief interaction can cause a long term change in behavior. They also investigate the neural effects of chronic social stress. Neurotrophins have altered expression in different pathologies such as epilepsy, Alzheimer's and Parkinson's diseases, and depression. Particularly in its association with forms of depression, social defeat may provide insights into the mechanisms by which these neurotrophin levels are related to depression. The results obtained will provide a foundation for developing an integrative model that can be applied across taxa. The fundamental goal of this proposal is to design and implement experiments that will facilitate my training as a developing molecular neuroendocrinologist and elucidate the mechanisms underlying socially- mediated modifications in social status behavior. The general research objectives are to: 1) characterize the relationship between neurotrophins and dominant and subordinate status, 2) test hypotheses related to the role of neurotrophins in the acquisition and maintenance of social status and its related behavior. Specifically, I propose two inter-related studies: 1) status-dependent differences in aggression, submissive behavior, plasma corticosterone concentrations, and neurotrophin brain mRNA expression and the relationships of these factors will be investigated, 2) direct experimental manipulations will assess the role of neurotrophins in the acquisition, consolidation, and maintenance of social status and its related behavior. These studies will aid in understanding a fundamental process by which social stress can induce persistent changes in the brain, such as is seen in patients with post-traumatic stress disorder and other mental health conditions that are exacerbated by social stress or helped by successful social interactions.