Neural Substrates /Socioemotional Disturbances /Develop.

描述（由申请人提供）：本提案的目标是了解 早期脑损伤如何影响短期和长期的发展 认知和社会情感功能。这种理解对于 治疗自闭症等神经发育障碍的方法， 与一系列的行为障碍有关， 由于儿童的许多神经障碍（癫痫，脑 麻痹、皮质发育不全等）。人体案例和实验分析 提出了一种假设，即内侧颞叶功能障碍， 尤其是杏仁核，是自闭症的一个病因因此 我们的目标是研究杏仁核的作用， 社会情绪行为的具体细分，并确定关键的 发育异常的发育期和神经触发因素 自闭症的动物模型第一个具体目标集中在影响 药理学诱导的杏仁核神经传递失衡， 婴儿动物的社会互动。已知的药物可以阻断或增强 GABA能或多巴胺能传输将被局部注入特定的 杏仁核和社会互动的实验 将观察动物。第二个具体目标是比较 药物（如目标I所述）具有亚区域离散病变效应 杏仁核，当受损的轴突保留兴奋性毒性病变，在婴儿 猴子第三个目标是评估早期长期癫痫发作的影响， 已知会破坏杏仁核及其投射网络的功能， 观察到的行为类别。这一目标是为了理解 为什么婴儿中的某些癫痫病症（例如，婴儿痉挛）引起 自闭症这些研究的一个重要方面将是分析 由各种解剖学上的原因引起的社会情绪障碍 特定部位的损伤伴随着认知功能的损害。 将使用标准化程序来评估 婴儿和幼年动物的社会情感相互作用， 评估他们对积极和消极刺激的情绪反应。认知 任务将包括并发视觉对象的歧视和视觉 跨模态联想和记忆。拟议研究的结果将 识别对调节社交和 情感互动，并决定发展的关键阶段 在此期间，杏仁核功能障碍（损伤，药物或癫痫发作）可能导致 长期的社会情绪异常这些信息将提供一个 设计治疗干预措施的基本原理， 纠正导致自闭症的潜在生物功能障碍， 相关的社会情绪障碍。

DESCRIPTION (provided by applicant): The goal of this proposal is to understand how early brain insults influence the short-term and long-term development of cognitive and socioemotional functions. This understanding is vital for the approach to neurodevelopmental disorders such as autism, and at the same time is relevant to an entire spectrum of behavioral disorders that emerge as a result of a host of neurological disturbances in children (epilepsy, cerebral palsy, cortical dysgenesis, etc.). The analysis of human cases and experiments in animals suggest the hypothesis that dysfunction in medial temporal lobes, and the amygdala in particular, is an etiological factor in autism. Therefore the goal of our proposal is to investigate the role of the amygdala and its specific subdivisions for socioemotional behavior and to identify the critical developmental periods and neural triggers for developmental abnormalities in an animal model of autism. The first Specific Aim concentrates on the effects of pharmacologically-induced imbalances in neurotransmission in the amygdala on social interactions in infant animals. Drugs known to either block or enhance GABA-ergic or glutamatergic transmission will be focally infused into specific subdivisions of the amygdala and social interactions in the experimental animals will be observed. The second Specific Aim is to compare the effects of drugs (as obtained in Aim I) with the effects of discrete lesions of subregions of the amygdala, when damaged by axon-sparing excitotoxic lesions, in infant monkeys. The third aim will evaluate the effects of early prolonged seizures, known to disrupt the function of the amygdala and its projection network, on the observed behavioral categories. This aim is directed to the understanding why certain seizure disorders in infants (e.g., infantile spasms) give rise to autism. An important facet of these studies will be the analysis of the extent to which socioemotional disturbances produced by various anatomically site-specific insults are accompanied by impairment in cognitive functions. Well standardized procedures will be used to evaluate various components of socioemotional interactions of infant and juvenile animals in dyads and to assess their emotional reactions to positive and negative stimuli. Cognitive tasks will include concurrent visual objects discrimination and auditory-visual crossmodal associations and memory. The results of the proposed studies will identify specific amygdaloid nuclei critical for regulation of social and emotional interactions and determine the critical stage(s) in development during which amygdala dysfunction (by lesions, drugs or seizures) can lead to long-term socioemotional abnormalities. This information will provide a rationale basis for the design of therapeutic interventions directed at correcting the underlying biological dysfunctions that give rise to autism and related socioemotional disorders.