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Krasnow Institute > Monday Seminars > Abstracts From Memory Molecules to Alzheimer's Disease Daniel L. Alkon, M.D. Our observations have related behavior of living animals to signal processing in neuronal networks and to subcellular molecular cascades. Our data have implicated molecular and biophysical mechanisms that are conserved in molluscan and mammalian species and thus could have relevance for human physiology. Cellular analyses of associative memory in the snail Hermissenda (Pavlovian conditioning), the rabbit (Pavlovian conditioning), and the rat (spatial maze learning, olfactory discrimination) revealed a cascade of cellular and subcellular events during memory formation: -Long-term transformation of GABAergic inhibition into excitation; -Elevation of Ca2+, DAG, and possibly AA; -Translocation of PKC; -Phosphorylation of the ARF-class G protein (as determined by molecular sequencing), cp20, which shows close functional homology with the Harvey-RAS protein; -Inactivation of voltage-dependent K+ channels; -Learning-specific regulation of gene transcription; and -Rearrangement of synaptic terminal branches. Such conservation suggested that these associative memory mechanisms may provide targets of dysfunction in Alzheimer's disease. Recent studies, in fact, revealed Alzheimer's-specific defects of K+ channels, IP3-mediated release of Ca2+, and metabolism of the G protein, cp20. Theoretical constructs based on these memory networks have also been mathematically described and are now being incorporated into computer-based artificial networks which have demonstrated powerful pattern recognition capabilities.
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