“We congratulate Roger Nicoll on being selected for this award,” said Robert Desimone, director of the McGovern Institute and chair of the selection committee. “It’s difficult to think of anyone who has done more to advance our understanding of synaptic plasticity, the basis of learning and memory.”
Nicoll’s main research goal for almost three decades has been to understand, at the cellular and molecular level, how electrical activity reshapes the brain’s connections. Much of his work has involved a form of synaptic plasticity known as long-term potentiation (LTP), an experimental procedure by which a burst of high-frequency electrical stimulation can induce a lasting increase in synaptic strength. LTP is most commonly studied within the hippocampus, a brain structure that is crucial for memory. Since its discovery in 1966, a growing body of evidence has indicated that the LTP reflects the natural mechanism by which experience leads to the formation and storage of new memories.
In a key paper published in 1988, Nicoll showed that LTP is triggered by a rise in calcium concentration within the postsynaptic terminal. This finding opened the door to understanding the molecular mechanism by which the strength of the synapse is changed. In subsequent papers, Nicoll went on to show that calcium exerts its effect by activating an enzyme called CAMKII, which in turn induces the postsynaptic neuron to respond more strongly to incoming signals.
Nicoll has continued to study the mechanisms of LTP ever since, and has made many further contributions to the field. He was among the first to demonstrate the existence of ‘silent synapses’ — structural connections that do not transmit signals until they are activated. In a recent collaboration with David Bredt, he showed that synaptic strength is adjusted through the insertion of glutamate receptors to synaptic sites, with the help of an accessory protein known as "stargazin."
Nicoll has made many other important discoveries over the course of his career. As a student, he discovered a key insight into mechanism of anesthesia, proposing the idea (now widely accepted) that general anesthesia involves the activation of GABAa receptors. He was the first to show that neurotransmitters, in addition to their rapid electrical effects, can activate chemical signaling pathways that underlie longer-term changes in the brain’s electrical properties. This type of signaling, known as neuromodulation, is ubiquitous within the brain and represents an important class of targets for psychiatric drugs. More recently he has studied the action of cannabinoids — natural signaling molecules in the brain whose effects are mimicked by cannabis. And in addition to his own contributions, Nicoll has been enormously influential as a mentor, having trained many of the other leading researchers in the field of synaptic physiology.
The McGovern Institute will award the Scolnick Prize to Nicoll on Thursday, April 19. At 4 p.m. he will deliver a lecture, titled “Deconstructing and reconstructing a synapse," to be followed by a reception, at the McGovern Institute in the Brain and Cognitive Sciences Complex, 43 Vassar St. (Building 46, Room 3002) in Cambridge. The event is free and open to the public.
The Scolnick Prize, awarded annually by the McGovern Institute, is named in honor of Dr. Edward M. Scolnick, who stepped down as president of Merck Research Laboratories in December 2002 after holding Merck's top research post for 17 years. Scolnick is now at the Broad Institute, where he established the Stanley Center for Psychiatric Research. He also serves as a member of the McGovern Institute’s governing board. The prize, which is endowed through a gift from Merck to the McGovern Institute, consists of a $70,000 award, plus an inscribed gift. Previous winners are Bruce McEwen (Rockefeller University), Lily and Yuh-Nung Jan (University of California, San Francisco), Jeremy Nathans (Johns Hopkins University), Michael Davis (Emory University), David Julius (University of California, San Francisco), Michael Greenberg (Harvard Medical School), Judith Rapoport (National Institute of Mental Health) and Mark Konishi (California Institute of Technology).