The Supramolecular Architecture of the Postsynaptic Density

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This project addresses the architecture of neuropil in the human cerebral cortex. Aim 1 uses material from surgically-resected temporal lobe to perform high-resolution quantitative electron microscopic studies of the structure of excitatory synapses, including synapses onto identified classes of interneurons. Using the same biological material, Aim 2 performs quantitative immunogold electron microscopy to define the architecture of a number of different molecules abundant in the postsynaptic density, focusing on proteins whose mutations are implicated in neuropsychiatric and neurodevelopmental disease, especially schizophrenia. Aim 3 performs work similar to that specified for Aims 1 and 2, but focusing on cortical organoids cultured in vitro. These results will make it possible to compare the structure and molecular organization of synapses in culture with synapses in intact brain.