Abstract: Series 112, Lecture 5
The Harvey Lectures Series 112 (2016—2017)
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Lecture #5: Thursday, March 16, 2017 — Watch Video of Lecture
Long-term Potentiation: A Cellular Model for Learning
Roger Nicoll, MD
Professor, Department of Cellular and Molecular Pharmacology
Professor, Department of Physiology
University of California, San Francisco
San Francisco, California
One of the most remarkable features of the brain is its ability to store vast amounts of information. For more than a century it has been proposed that changes in the strength of synaptic connections underlying learning and memory. However, it was not until the discovery of long-term potentiation (LTP) in 1966, in which brief high frequency synaptic stimulation in the hippocampus results in a long lasting increase in synaptic strength, that there was experimental evidence supporting such a proposal. LTP has remained to this day the most compelling cellular model for learning and memory. Great strides have been made in our understanding of the cellular and molecular mechanisms underlying LTP. It has long been known that NMDA receptor activation followed by CaMKII activation is required for the induction of LTP. More recently it has been shown that CaMKII activation results in the rapid recruitment of AMPA receptors to the synapse. This recruitment is independent of AMPA receptor subunit type. Remarkably the kainate subtype of glutamate receptor can substitute for AMPA receptors. These unexpected results have required a reappraisal of the role of CaMKII. Rather than targeting and modifying AMPA receptors, we propose that CaMKII activation leads to a rapid creation of slots in the PSD, which capture receptors that freely diffuse on the surface membrane. Many questions remain. For instance, what maintains these slots over prolonged periods of time?