Vicarious Neural Activity, Genetic Differences and Social Fear Learning

项目摘要 自闭症谱系障碍（ASD）的特征是几个广泛的诊断特征，其中最突出的是无法进行社交或情感互惠。这项拨款提案的长期目标是确定大脑中的特定部位，这些部位可用作开发更有效和更具体的药物治疗干预措施的靶点，用于治疗ASD等社会疾病。所提出的实验将利用自闭症模型（即，BALB/cJ-C57 BL/6 J社交性模型）来阐明哺乳动物脑中参与对他人的应激的检测和响应的区域。 这项拨款提案的研究策略是基于这样一个前提，即建立一个强大的社会性模型将产生关于哺乳动物社会大脑在健康和疾病状态下的基本知识。 本提案的具体目标可以在PI培训计划的背景下总结： 具体目标1 -描述表达替代代谢和转录应激反应的大脑区域，这将为PI提供培训机会，以获得代谢脑图谱和诱导型转录因子免疫组织化学方面的专业知识。 具体目标2 -采用局部脑失活程序来调节对其他人的应激诱导敏感的行为反应，这将使PI获得用于部位特异性可逆脑失活技术的程序的专业知识。 具体目标3 -表征个体神经元对提示他人压力的提示的生理活动，这将为PI提供最先进的电生理记录技术方面的出色培训体验。

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.