Leon Cooper

Toward a Cellular and Molecular Basis for Memory: Theory and Experiment


Abstract

I retrace the journey that has taken me from abstract mathematical representations of memory to biochemical pathways that provide the likely cellular and molecular basis for learning and memory storage. It is a journey marked by an interaction between theory and experiment, the norm in physics since Galileo, but still novel and not universally accepted in neuroscience. I will show how this interaction has proved to be extraordinarily fruitful. Theory has suggested experiments that have uncovered new phenomena such as: Long Term Depression (LTD), bi-directional synaptic modification dependent on the depolarization of the post-synaptic cell and the sliding modification the threshold in agreement with BCM synaptic modification function. This has provided experimental verification of the postulates of the BCM theory of synaptic plasticity. Theory has also clarified connections between seemingly unrelated observations in different brain regions such as LTD/LTP in hippocampus to reverse suture results in visual cortex.

We have shown that one underlying calcium dependent mechanism can account for the various methods of inducing synaptic plasticity. Cellular and molecular mechanisms that underlie this synaptic plasticity have been proposed, and some of these have been confirmed experimentally. The interaction of local and global modulatory signals, the probable basis for memory consolidation, as well as the implication of LTD mechanisms in such pathologies as the Fragile X Syndrome are being explored.

Among the topics that will be discussed are the BCM theory of synaptic plasticity, its experimental confirmations, a unified model of calcium dependent plasticity, as well as cellular and molecular mechanisms underlying synaptic plasticity and thus learning and memory storage.


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