Professor, Department of Physiology, University of Toronto; Krembil Family Chair of Alzheimer’s Research; Senior Investigator, LTRI, Mount Sinai Hospital, Canada; Professor of Neuroscience in Anatomy, University of Bristol, UK; Affiliated Scientist, Krembil Research Institute
Graham Collingridge, FRS, CBE, is the Director of the Tanz Centre for Research in Neurodegenerative Diseases (CRND), a Professor in the Department of Physiology at the University of Toronto, and a Senior Investigator at the Lunenfeld-Tanenbaum Research Institute at Mount Sinai Hospital, Toronto. Educated in the UK, he received a BSc in Pharmacology from the University of Bristol and a PhD from the School of Pharmacy, University College London in the field of neuroscience. Following postdoctoral appointments at the University of British Columbia (UBC), in Vancouver, and at the University of New South Wales, in Sydney, he returned to the UK to establish a laboratory at the University of Bristol. He has served as Chairs of the Department of Pharmacology at the University of Birmingham (UK), the Department of Anatomy at the University of Bristol and, most recently, the Department of Physiology at the University of Toronto. He was the founding Director of the MRC Centre for Synaptic Plasticity at the University of Bristol from 1999 until 2012 and retains a post within the School of Physiology, Pharmacology and Neuroscience in Bristol. Collingridge has held visiting ships at UBC and at Seoul National University, in South Korea. He has served as the President of the British Neuroscience Association and is currently the President of the Canadian Physiological Society. He served as Editor-in-Chief of Neuropharmacology from 1993 until 2010 and is currently a reviews editor for Molecular Brain. He is a Founder Fellow of the European DANA Alliance and a Founder Fellow of the Academy of Medical Sciences (UK). In 2001 he was elected a Fellow of The Royal Society. He serves on the scientific advisory board of Hello Bio and Brain Canada. Amongst the many recognitions for his research, Collingridge was, in 2016, a co-recipient with s Tim Bliss FRS and Richard Morris FRS of The Brain Prize, which is often regarded as the “Nobel Prize of Neuroscience." In 2019, he was appointed a Commander of the Order of the British Empire (CBE) in the Queen’s birthday honours.
As a PhD student, Collingridge became fascinated by the actions of the brain’s major excitatory neurotransmitter, L-glutamate, at synapses, the connections between neurons. As a postdoctoral fellow in Vancouver, working in the laboratory of Professor Hugh McLennan, he showed that L-glutamate acting on a specific protein, known as the N-methyl-D-aspartate receptor (NMDAR), can trigger changes in the strength of synaptic connections (i.e., synaptic plasticity). This mechanism has since been shown to be used extensively for many forms of learning and memory in mammals, including humans. In Bristol, he identified the mechanism by which the NMDAR triggers these alterations in synaptic plasticity, thereby helping to provide a molecular explanation for the operation of Hebbian synapses. He also showed how excessive NMDAR activation is detrimental to optimal synaptic plasticity and, working with Merz Pharma, demonstrated how a drug that interacts with the NMDAR, memantine, could correct aberrant synaptic plasticity. This formed the key step in the preclinical development of memantine, which is now used extensively to slow the progression of dementia. Subsequently, in collaboration with colleagues at the MRC Centre for Synaptic Plasticity and at UBC, Collingridge established some of the biochemical pathways that are activated in neurons when NMDARs are stimulated. Notably he showed that the weakening of synaptic connections involves a cascade involving glycogen synthase kinase (GSK-3) and tau. He helped show how this pathway could be triggered by toxic species of aggregates of amyloid beta, proving a molecular link between the amyloid (plaques) and tau (tangles) theories of Alzheimer’s disease. This mechanistic understanding has led to the hypothesis that Alzheimer’s disease is a dysregulation of synaptic plasticity. More specifically, that a normal brain function, triggered by NMDARs, to weaken and eliminate synapses (pruning) is driven into hyper-drive by pathological alterations, which may involve genetic changes, environmental insults or, commonly, a combination of both. The Tanz CRND, with its multidisciplinary approaches to multiple neurodegenerative diseases provides the ideal environment to test this overarching hypothesis. Collingridge is currently aiming to better understand synaptic plasticity in health and disease states and to help develop improved medications that work via interacting with the NMDAR.
