Vicarious Neural Activity, Genetic Differences and Social Fear Learning

项目摘要 自闭症谱系障碍(ASD)的特点是几个广泛的诊断特征，其中最突出的是无法进行社会或情感上的相互作用。这项拨款提案的长期目标是确定大脑中可用作目标的特定部位，以开发更有效、更具体的药物治疗干预措施，以治疗以自闭症等疾病为特征的社会疾病。这项拟议的实验将利用自闭症模型(即BALB/CJ-C57BL/6J社交模型)来阐明哺乳动物大脑中参与检测和反应他人压力的区域。 这项拨款提案的研究策略是基于这样一个前提，即发展一个健壮的社交模型将产生关于哺乳动物在健康和疾病状态下的社交大脑的基本知识。 本提案的具体目标可在PI培训计划的范围内总结： 特定目标1-描绘大脑中表达对应激的替代代谢和转录反应的区域，这将为PI提供一个培训机会，以获得代谢脑图谱和诱导转录因子免疫组织化学方面的专业知识。 具体目标2-使用局部脑失活程序来调节对他人压力诱导敏感的行为反应，这将使PI获得用于特定部位的可逆脑失活技术的程序专业知识。 具体目标3-表征单个神经元在呈现指示其他人应激的提示时的生理活动，这将使PI在最先进的电生理记录技术方面获得良好的训练体验。

Project Summary Autism spectrum disorders (ASDs) are characterized by several broad diagnostic features, with one of the most prominent being an inability for social or emotional reciprocity. The long-term objective of this grant proposal is to identify specific sites in the brain that can be used as targets for the development of more effective and more specific pharmaco-therapeutic interventions for social ailments that characterize conditions like ASD. The proposed experiments will utilize a model of autism (i.e., the BALB/cJ-C57BL/6J model of sociability) to elucidate regions of the mammalian brain that are involved in the detection and response to stress in others. The research strategy for this grant proposal is based on the premise that development of a robust model of sociability will generate fundamental knowledge regarding the mammalian ¿social brain¿ in both healthy and diseased states. The specific aims of this proposal can be summarized within the context of the training program for the PI: Specific Aim 1 - Delineate regions of the brain that express vicarious metabolic and transcriptional responses to stress, which will provide the PI with a training opportunity to acquire expertise in metabolic brain mapping and inducible transcription factor immunohistochemistry. Specific Aim 2 - Employ a localized brain inactivation procedure to modulate a behavioral response that is sensitive to the induction of stress in others, which will allow the PI to acquire expertise in procedures that are used for site-specific, reversible brain inactivation techniques. Specific Aim 3 - Characterize the physiological activity of individual neurons in response to presentation of cues that indicate stress in others, which will give the PI an excellent training experience in state-of-the-art electrophysiological recording techniques.