Neural Substrates of Socioemotional Development

描述（由申请人提供）：本申请中提出的研究和职业发展计划将扩展候选人在神经药理学，正常和异常社会情感发展，癫痫学和核磁共振成像（MRI）方面的专业知识，以应用于神经发育障碍，如自闭症，智力迟钝和脑瘫。提出的研究计划将利用最近的证据，即内侧颞叶，特别是杏仁核的功能障碍可能是自闭症的一个病因因素。该应用程序的目的是研究杏仁核及其特定分支在社会情感行为中的作用，并确定自闭症动物模型中发育异常的关键时期和神经触发因素。具体目标1集中在药理学诱导的杏仁核神经传递失衡对幼龄动物社会互动的影响。特异性目标2将比较药物的效果（如在目标1中获得的）与杏仁核亚区离散损伤的效果，这些损伤是由保留轴突的病变造成的。特异性目标3将评估早期长时间癫痫发作对神经发育行为结果的影响，已知癫痫发作会破坏杏仁核及其投射网络的功能。为实现这些目标而设计的实验将为候选人提供一个机会，在结合使用药理学，生理学和MRI方法来研究动物模型方面获得理论和实践专业知识。该候选人在行为研究方面的背景将被应用于分析婴儿和幼年动物的社会情感互动的各种组成部分，并评估它们的认知功能。职业发展计划将促进候选人的研究能力和范围的实质性转变，这样她就有可能建立一个独立的研究项目，致力于识别自闭症和其他发育障碍的神经机制。评估动物模型中药物干预的多因素影响的能力将为候选人从事神经发育障碍动物模型的研究做好准备，并将她的研究技能置于药理学，癫痫学和生理学的背景下。结构化的活动和短期课程将指导这些领域的专业知识的发展，这些领域对于拟议的研究以及作为一个多才多艺的神经科学家的候选人的长期职业发展是必要的。

DESCRIPTION (provided by applicant): The research and career development plans proposed in this application will expand the candidate's expertise in neuropharmacology, normal and abnormal socioemotional development, epileptology, and magnetic resonance imaging (MRI) as applied to neurodevelopmental disorders such as autism, mental retardation, and cerebral palsy. The Research Plan proposed will take advantage of the recent evidence that dysfunction in medial temporal lobes, and the amygdala in particular, may be an etiological factor in autism. The goal of the application is to investigate the role of amygdala and its specific subdivisions for socioemotional behavior, and to identify the critical periods and neural triggers for developmental abnormalities in an animal model of autism. Specific Aim 1 concentrates on the effects of pharmacologically induced imbalances in neurotransmission in amygdala on social interactions in infant animals. Specific Aim 2 will compare the effects of drugs (as obtained in Aim 1) with the effects of discrete lesions of subregions of amygdala, damaged by axon-sparing lesions. Specific Aim 3 will evaluate the effects of early prolonged seizures, known to disrupt the function of amygdala and its projection network, on the neurodevelopmental behavioral outcomes. The experiments designed to pursue these aims will provide an opportunity for the candidate to gain both theoretical and practical expertise in the combined use of pharmacological, physiological, and MRI approaches to the study of the animal models. The candidate's background in behavioral research will be applied to the analyses of various components of socioemotional interactions of infant and juvenile animals in dyads and the assessment of their cognitive functions. The career development plan will facilitate a substantial shift in the candidate's research capabilities and scope, so that it will become possible for her to build an independent research program devoted to the identification of neural mechanisms underlying autism and other developmental disorders. The ability to evaluate the multifactorial impact of pharmacological interventions in animal models will prepare the candidate to pursue research on animal models of neurodevelopmental disorders and place her research skills in the context of pharmacology, epileptology, and physiology. Structured activities and short courses will guide the development of expertise in these areas necessary for the proposed studies as well as for the long-term career advancement of the candidate as a versatile neuroscientist.