THE NEUROANATOMICAL BASIS OF SOCIAL-AFFECTIVE DEFICITS IN AUTISM

自闭症的神经病理学研究结果一直涉及海马体和杏仁核，这两个关键的边缘系统结构在许多皮层区域都有特定但广泛的联系。虽然海马体在陈述性记忆和短期记忆过程中具有重要功能，但相比之下，杏仁核与情绪、恐惧、焦虑有关，并且对于与3eers和环境的社会互动至关重要。 和情感行为虽然海马体和杏仁核是许多研究的主题， 虽然目前正在进行研究，但这两个关键大脑区域的直接和间接皮层连接在自闭症中还没有得到很好的研究。因此，本研究将探讨六个关键的皮质区，包括两个在额叶（内侧和眶额皮质），扣带回（前，后扣带回和压后皮质）和颞叶梭状回的梭状面区，其中每一个都有重要的联系，无论是在杏仁核，杏仁核或两者。这一假说认为，这些边缘皮质内的回路发生了改变，导致了自闭症患者的社会情感行为缺陷。将通过6个皮质中的细胞病理学标准尼氏染色研究细胞结构和皮质细胞结构。因为现在看来苯二氮卓类药物结合的异常 位点和GABA-A受体已被确定在海马，GABA能将在六个皮质区使用各种方法进行调查。免疫细胞化学将定量皮质GABA能中间神经元的亚群，并利用针对三种类型的GABA能转运蛋白（摄取位点）的抗体评估功能活性。此外，体外多浓度配体结合将量化结合密度和结合苯二氮卓类和GABA-A位点以及三种类型的多巴胺能受体的亲和力，这是自闭症谱系中涉及的另一种递质系统。最后，动态 利用针对两种类型神经胶质细胞的抗体来评估自闭症个体脑内的状态：小胶质细胞和星形胶质细胞。在神经病理学改变的部位的小胶质细胞聚集将是研究的焦点，假设自闭症是一个持续的过程，而不是一个静态的障碍。

Neuropathological findings in autism have consistently implicated the hippocampus and amygdala, two key limbic system structures with specific but wide-ranging connections throughout many cortical regions. While the hippocampus has important functions in declarative and short term memory processes, the amygdala in contrast has been implicated in emotions, fear, anxiety and is critically important for social interaction with 3eers and the environment, in autism, individuals have difficulties with declarative memory and with socioemotional and affective behavior. Although the hippocampus and amygdala are the subject of many ongoing research studies, the direct and indirect cortical connectivity of these two key brain areas have not been well studied in autism. Thus, the present study will investigate six key cortical areas including two in the frontal lobe (medial and orbital frontal cortex), three areas in the cingulate gyrus (anterior and posterior cingulate and retrosplenial cortex) and the temporal lobe fusiform face area in the fusiform gyrus, each of which have important connections with either the hippocarnpus, amygdala or both. The hypothesis is that the circuitry within these limbic cortices is altered contributing to the social affective behavioral deficits in autism. The cellular structure and cortical cytoarchitecture will be studied via standard Nissl stains for cellular pathology in the six cortices. Since it now appears that abnormalities in benzodiazepine binding sites and GABA-A receptors have been identified in the hippocampus, the GABAergic will be investigated in the six cortical areas using a variety of methods. Immunocytochemistry will quantify subpopulations of cortical GABAergic intemeurons and assess the functional activity utilizing antibodies dierected against three types of GABAergic transporters (uptake sites). In addition, in vitro multiple concentration ligand binding will quantify the density of binding and affinity to bind benzodiazepine and GABA-A sites as well as three types of serotonergic receptors, another transmitter system implicated in autistic spectrum. Finally, the dynamic state within the brain of autistic individuals will be assessed utilizing antibodies toward two types of neuroglia: microglia and astrocytes. Microglial aggregations at sites of neuropathological changes wilt be a focus of the study with the hypothesis that autism is an ongoing process and not a static disorder.