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Components of the cell are positioned and compartmentalized with exquisite precision, but the functional significance of this organization has only recently been recognized. Spatial complexity is especially prominent within the nervous system. My research addresses the organization of excitatory synapses in rodent neocortex and hippocampus. Techniques routinely used in my lab include high-resolution and quantitative light- and electron microscopic immunocytochemistry.
We performed a number of studies using light microscopic immunocytochemistry and immunogold EM to examine the relationship of AMPA and NMDA glutamate receptors to the synaptic active zone. We continue this basic line of research: Proteomics studies have identified over 100 proteins associated with the postsynaptic density (PSD). We are using quantitative immunogold methods and high-resolution electron tomography to examine the organization of a variety of these proteins, to elucidate the supramolecular architecture of the PSD. We want to use this information to explore how the organization of molecules within the synapse may help to regulate postsynaptic signaling pathways. For example, calcium ions entering through NMDA receptor channels may modify synaptic activity. Might the targets of this calcium entry (e.g., CaMKII, nNOS, or calcium-dependent adenylyl cyclase) be situated close to the NMDA pore, suitably positioned to respond selectively to calcium entry through that pore? Likewise, might specific enzymes (e.g., PKA) that can modulate AMPA receptors be held close to these receptors?
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Journal of Nuclear Cardiologyno. 2 (2019): 374-386
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