PROJECT III ABSTRACT Wlliams Syndrome is a rare neurodevelopmental disorder with a characteristic behavioral profile that includes an abundance of affectivity or hypersociability. Neuroimaging findings from Project IV indicate that the atypical affiliative behavior in WS is related to enhanced development of anterior regions including parts of the frontal lobe and the temporal lobe. However, no anatomical information is currently available at the microstructural level for any parts of the social brain circuitry in WS. Project 111 aims to identify the fundamental microstructural differences that account for the observed augmentation of the social brain in WS, including whether numbers of neurons, degree of arborization or distribution of specific neuronal subpopulations constitute the factors underlying the observed changes in the frontal lobe and the amygdala. Specifically, we will investigate: (1) the differences in the neuronal number and cell body size that contribute to observed changes in density, (2) the differences in connectivity inferred by cellular arrangement of neurons within cortical layers and (3) expressed by degree of arborizations and morphology of neurons, (4)differences in distribution of elemental factors associated with synaptic activity and cellular metabolism. Using a combination of well established techniques including stereology and the Golgi method, we will address fundamental questions of the microarchitecture in WS social brain regions. In additional, we employ a groundbreaking technique of synchrotron-based x-ray fluorescence imaging to explore the possibility of altered distribution of specific neuronal subpopulations in WS as compared to TD. Our findings will provide a crifical neuroanatomical foundation to this Program Project and are essential components to integrating across biological scales and forming our comprehensive picture of the WS social phenotype.
The proposed research will identify and map the neural microcircuitry underlying specific social behaviors in the WS. The findings will also assist in understanding the neurobiology of social cognition in healthy subjects and provide a neurobiological framework relevant to the design of treatments of neuropsychiatric disorders of social behavior.
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