Neuroplasticity of Social Learning

描述（由申请人提供）：创伤性事件和慢性压力与压力相关精神病理的发展有关。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，将其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压力源，可以抑制社会地位低或长期处于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延迟）。这些研究着眼于神经营养素在社会地位中的作用，以及短暂的相互作用如何导致长期的行为改变。他们还研究了长期社会压力对神经系统的影响。神经营养因子在癫痫、阿尔茨海默病和帕金森病以及抑郁症等不同病理中表达改变。特别是它与抑郁症的联系，社会失败可能提供了这些神经营养因子水平与抑郁症相关的机制的见解。研究结果将为建立一个适用于不同分类群的综合模型奠定基础。本提案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训练，并阐明社会地位行为中社会介导的改变的潜在机制。总的研究目标是：1)表征神经营养因子与支配地位和从属地位之间的关系；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的假设。具体来说，我提出了两项相互关联的研究：1)攻击行为、顺从行为、血浆皮质酮浓度和神经营养因子脑mRNA表达的状态依赖性差异以及这些因素之间的关系将被研究；2)直接实验操作将评估神经营养因子在社会地位的获得、巩固和维持及其相关行为中的作用。这些研究将有助于理解社会压力能够诱发大脑持续变化的基本过程，例如在创伤后应激障碍和其他精神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.