Neural Substrates /Socioemotional Disturbances /Develop.

描述(由申请人提供)：本提案的目的是了解 早期脑侮辱如何影响儿童精神分裂症的短期和长期发展 认知和社会情感功能。这一理解对于 自闭症等神经发育障碍的治疗方法，同时 与一系列行为障碍有关，这些行为障碍表现为 儿童一系列神经功能障碍的结果(癫痫、脑部疾病 瘫痪、皮质发育不全等)。人体病例和实验的分析 在动物身上提出了内侧颞叶功能障碍的假设， 尤其是杏仁核，是自闭症的一个病因。因此 我们建议的目标是研究杏仁核和它的 社会情绪行为的具体细分并确定关键的 儿童发育异常的发育期和神经触发因素 自闭症动物模型。第一个具体目标集中在 药物诱导的杏仁核神经传递失衡 幼年动物的社会互动。已知可阻断或增强的药物 GABA能或谷氨酸能传递将局部注入特定的 杏仁核的细分与实验中的社会相互作用 动物将被观察。第二个具体目标是比较 具有分区域离散病变作用的药物(在目标一中获得) 婴幼儿杏仁核被轴突保护的兴奋性毒性损伤 猴子。第三个目标将评估早期延长癫痫发作的影响， 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。这个目的是为了理解 为什么婴儿中的某些癫痫发作障碍(例如婴儿痉挛)会引起 自闭症。这些研究的一个重要方面将是分析 由不同的解剖学产生的社会情感障碍 特定地点的侮辱伴随着认知功能的损害。 将使用良好的标准化程序来评估 婴幼儿和幼年动物在双亲和双亲中的社会情绪互动 评估他们对积极和消极刺激的情绪反应。认知 任务将包括同时识别视觉对象和听觉-视觉 跨模式联想和记忆。建议的研究结果将会 确定特定的杏仁核对调节社会和 情感互动和决定发展的关键阶段(S) 在此期间，杏仁核功能障碍(由于损伤、药物或癫痫发作)可导致 长期的社会情绪异常。此信息将为您提供 设计针对以下目标的治疗干预措施的理论基础 纠正导致自闭症和 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.