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The Endocytic Pathway in Normal and Degenerating Mammalian CNS Neurons.
Neurotransmission relies on the proper trafficking of synaptic vesicles (SVs) in nerve terminals. In the SV cycle, depolarization-induced calcium entry triggers the fusion of SVs with the plasma membrane. Subsequently, the SV membrane, along with essential membrane-bound SV proteins, must undergo recycling in order to replenish nerve terminals with new fusion-competent vesicles. This process is crucial to prevent plasma membrane expansion and SV depletion, both of which would impair neurotransmission. A major recycling pathway involves the retrieval of membrane through clathrin-mediated endocytosis, although other pathways (e.g. “kiss and run”) have been described. Our laboratory studies the molecular mechanisms governing the recycling process in mammalian CNS synapses using molecular, cellular and genetic approaches. As a model system, we largely use primary cultures of cortical and hippocampal neurons prepared from rodent brain. Our research efforts focus on how protein-membrane (or lipid) interactions regulate the ability of vesicles to fuse, bud and travel within normal nerve terminals as well as within synapses from animal models for disorders, such as Alzheimer’s disease and Down syndrome.