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。大多数应激相关障碍的动物模型使用严格控制的但人为的应激源，将其扩展到更自然的相关应激源是至关重要的。社会压力是一种更自然的压力源，可以抑制社会地位低的动物或处于长期社会压力下的动物的生殖功能(如缺乏求偶行为、性腺功能延迟或青春期开始延迟)。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交压力对神经的影响。神经营养因子在癫痫、阿尔茨海默氏症和帕金森氏症以及抑郁症等不同的病理中改变了表达。尤其是在它与各种形式的抑郁症的联系上，社交失败可能会让人们对这些神经营养素水平与抑郁症相关的机制有深入的了解。所获得的结果将为开发可跨分类群应用的综合模型提供基础。这项提议的基本目标是设计和实施实验，以促进我作为一名发展中的分子神经内分泌学家的培训，并阐明社会中介改变社会地位行为的潜在机制。总体研究目标是：1)表征神经营养因子与支配地位和从属地位的关系；2)检验有关神经营养因子在社会地位及其相关行为的获得和维持中的作用的假说。具体地说，我提出了两项相互关联的研究：1)攻击性、顺从行为、血浆皮质酮浓度和神经营养素脑mRNA表达的地位依赖差异将被调查，以及这些因素之间的关系；2)直接的实验操作将评估神经营养因子在获得、巩固和维持社会地位及其相关行为中的作用。这些研究将有助于理解社会压力可导致大脑持续变化的基本过程，例如创伤后应激障碍和其他精神健康状况的患者，这些疾病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.