Studies on Plasticity and Neurodegeneration in Rat Hippocampus

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Hippocampus plays an essential role in learning and memory. Numerous studies have been directed at understanding the mechanisms underlying these processes. In particular, the role of protein synthesis has been extensively debated. Hippocampus is also extremely vulnerable to numerous stressors including excitotoxicity and stroke, and the mechanisms underlying vulnerability of hippocampal neurons to stress are still not completely understood. Studies here are concerned with both problems. Activity-dependent activation of excitatory synapses results in cell membrane depolarization, calcium influx, brief activation of calcium-dependent signaling cascades, changes in dendritic cytoskeleton and protein synthesis; on the other hand, excessive activation of excitatory synapses elicits excessive calcium influx, prolonged activation of calcium-dependent proteases such as calpain, breakdown of calcium homeostasis and neuronal damage. While my studies cover both neurodegeneration and synaptic plasticity, the common pathways they share suggest that depending on activation conditions, the same pathway might act on distinct substrates and produce quite different results.