Inspiration and luck drove Graham Collingridge, winner of Brain Prize

The neuroscientist and new chair of physiology at the University of Toronto explains his work on human memory that led to €1-million prize.

University of Toronto neuroscientist Graham Collingridge was awarded the prestigious Brain Prize earlier this month. Collingridge's focus on a brain receptor called NMDA could shed light on how conditions such as Alzheimer's disease impair memory.

Memory is the indispensable human faculty — the metaphysical foundation of all science, music and literature. But memories also have a physical dimension. They exist along the neurochemical connections that wire our brains in astonishing complexity.

For his work in describing the physiological mechanisms that create and keep memories, neuroscientist Graham Collingridge was one of three researchers awarded the €1-million Brain Prize this month. The newly minted chair of the University of Toronto’s physiology department spoke to the Star about his work and his recent move to Canada. Following is an edited version of the conversation.

How did you decide on the brain as your organ of interest?

I got really interested in science (during) my schooling in the U.K. My science teachers were fantastic. I chose a degree at Bristol University in pharmacology, because I was interested in both biology and chemistry. And it was just chance that the scientists in that department were all interested in neuroscience.

And when I was looking for my first post-doctoral position I was attracted to work in the (UBC) laboratory of Hugh McLennan, who was an eminent neuroscientist in Vancouver. But it was really my schoolteachers, going back to when I was about 10. (One teacher) really inspired me to do biology. Then as I went through my high school, I had fantastic chemistry and physics teachers.

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You gained international recognition for your work at Bristol, where you spent most of your career. Why did you make the move to Toronto in 2015?

One of the main factors was I had come over to Toronto a couple of years ago now to give a talk (at) a retirement symposium. And at that point … they were looking for a new chair at (U of T’s) department of physiology. And a few of my colleagues who I had long-standing collaboration with were already in Toronto. (One) was an eminent Alzheimer’s researcher, Peter St George-Hyslop.

They all said to me, “Well look, we’re all collaborating. Are you interested in the possibility of this job?” And the more I thought about it and the more I talked to people and the more I looked around Toronto, the more attractive it became. I realized that it’s a fantastic research environment. What I think is unique in the world is that you’ve got one major research-intensive university … with these very close associations with research institutes embedded within these outstanding (teaching) hospitals. I was offered a joint position in one of these hospitals, Mount Sinai (in the Lunenfeld-Tanenbaum Research Institute).

You were well aware prior to leaving Bristol of the scientific reputation of this city, of the U of T and the calibre of research here?

Absolutely, yes.

You’re looking at the mechanisms of memory. In particular you study a process called long-term potentiation, or LTP, that establishes memories in the brain. Can you describe this for us?

Memories are somehow stored in our brains and our brains consist of billions of nerve cells or neurons. On average there are probably 1,000 to 10,000 connections between one nerve cell and the next. Those connections are called synapses.

It’s been widely assumed for many years that memory is stored at these synapses. The most famous quote in neuroscience … essentially said when you have two nerve cells firing at the same time, they will strengthen their connections: “cells that fire together wire together.”

That (firing is achieved with the use of) the brain’s major neurotransmitter, a simple amino acid called glutamate. The electric impulses from a nerve cell will cause glutamate to be released and that will cross this little synapse and act on the neurons on the other side. The way it does this (is) it binds to specific protein molecules called receptors. (Earlier researchers) identified some of these different receptors, one of which was called the NMDA receptor. And what I did as a post-doc (researcher) was ask: is it possible that these different receptors for glutamate could have a specific role in the process of LTP? It turned out that it was the NMDA receptor that was the trigger. I identified NMDA’s role in this mechanism. And at that point I decided, “That’s what I’m going to spend my career working on.”

You’ll do important work in Alzheimer’s disease at Mount Sinai. How do you believe NMDA is involved in this ailment?

We now know the NMDA receptor is involved in both increasing synaptic strength, which is the process of long-term potentiation, and decreasing synaptic strength, known as long-term depression or LTD. What I believe is happening is that in the early stages of neurodegenerative conditions such as Alzheimer’s, you’re getting a dysregulation of this process. You’re getting more LTD. Eventually, this will cause elimination of synapses.

You have four children, ages 6 through 21. Do any of them share your scientific calling?

One of them is interested in psychology. I think the others looked at their poor dad and decided to go into business.