Roger Nicoll, Department of Cellular and Molecular Pharmacology, University of California at San Francisco, USA
CaMKII and synaptic memory
I will begin by introducing models of how the brain stores information. I will then introduce long-term potentiation (LTP) and summarize the essential role of AMPA receptor auxiliary subunits, referred to as TARPs, and their binding to the synaptic scaffolding protein PSD-95. In the mid 1980’s Crick and Lisman independently proposed a two-step model for molecular storage. The first step requires a multimeric protein whose subunits phosphorylate each other. The second step requires that the multimeric protein can undergo subunit exchange, such that naïve unactive subunits can be incorporated into the active multimeric protein. The second step solves the problem of memory storage in the face of molecular turnover. Much of the talk will focus on CaMKII and the maintenance of LTP (memory). I will present physiological evidence indicating that CaMKII satisfies all the expectations proposed by Crick and Lisman.
Roger Nicoll received his medical training at the University of Rochester School of Medicine and his research training at the National Institutes of Health. Following work with Nobel laureate John Eccles he joined the University of California at San Francisco where he has remained. Dr. Nicoll has been a world leader in elucidating the basic mechanisms underlying synaptic transmission and synaptic plasticity in the mammalian brain. His numerous contributions over the last 40 years have laid the foundation for much of our understanding of how neurons communicate and the adaptations in synaptic communication that underlie normal and pathological behavior. In experiments of unusual clarity and rigor, he has revealed the subtlety and complexity of this signaling. Perhaps his most important contribution has been in elucidating a number of the key cellular and molecular steps by which the brain stores information. His recent work focuses on CaMKII in long term information storage. For his contributions he has received numerous awards including 3 NIH MERIT awards, election to the National Academy of Science, election to the American Academy of Arts and Sciences, the Grass Lecture (SfN), the Gerard Prize (SfN) and the Warren Alpert Foundation Prize (Harvard).