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Krasnow Institute > Monday Seminars > Abstracts EXON-BASED TRANSCRIPTIONAL ACTIVATORS: James L. Olds The general consensus among neurobiologists and hence most network researchers is that the dendritic spines (the small protuberances that number about 20,000 to a cortical pyramidal cell) are the loci for the synaptic weight changes that probably subserve associative memory formation. Evidence from our laboratory and others suggests that complex sequences of biochemical reactions, leading from neurotransmitters interacting with spine-localized receptors to the activation of secondary and tertiary messenger systemsand eventually to the neuron's genomic machinery, are the biological phenomena which, in their totality, represent the engram. The key to this engram is twofold. On the one hand, the specificity lies in the sequence of chemical reactions. Any single one of those reactions is in fact generic to almost all eukaryotic cells in organisms that range from yeast to human beings, but taken together, and in the correct order, their probability of occurence under conditions other than those of associative mnemonic function become vanishingly small. The second aspect of the specificity lies in the spatial distribution of the spines themselves, spread out like the leaves on a huge elm tree. Each of these spines is related to each of the others in an essentially unique way. It is the spatial localization of spines that, with the sequence of biochemical reactions refered to above, permits complex brains to encode, classify and recall vast amounts of information. In this presentation, we consider a novel mechanism by which a protein that acts both in the nucleus, as a transcriptional factor, and in the dendrites, as a polyribisomal translational factor, could direct some aspects of the specificity required for associative learning. We additionally consider some evidence from our own laboratory that the learning-associated protein, cp20 may play such a role.
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