Professor John O’Keefe discovered the brain region responsible for mapping and navigating the environment. And his explorations continue…

Terrific, delighted, and grateful were among the joyful words from Professor John O’Keefe upon hearing that he would be awarded the 2014 Nobel Prize in Physiology or Medicine. O’Keefe, who is at University College London (UCL), shares the prize with May-Britt and Edvard Moser from the Norwegian University of Science and Technology. O’Keefe has known the Mosers since they were students and their work builds on his foundational findings.

More than 40 years ago, O’Keefe and collaborators found that hippocampal brain cells—now called place cells—are activated when rats explore their surroundings. “We were quite surprised at what we found and it led to the hypothesis that the hippocampus is involved in spatial orientation,” says O’Keefe. The activation pattern of place cells reflects the external surroundings, and different environments lead to different patterns. These and other results demonstrated that hippocampal place cells create an internal map for navigation and a sense of place.

The work applies to humans as well as rodents. The hippocampus is involved in memory and shows damage early in Alzheimer’s disease. People with Alzheimer’s tend to get lost, even in familiar places. O’Keefe, who directs the new Sainsbury Wellcome Centre in Neural Circuits and Behaviour at UCL, says, “We hope that some of our work will translate into things that are useful and beneficial. I’m interested in Alzheimer’s disease and continue to pursue research along those lines.” O’Keefe does basic research, but if appropriate industry partnerships and translational opportunities arise, he says, “we’ll be happy to look into them.”

Thinking and working hard

Colin Lever, senior lecturer in cognitive neuroscience, Durham University, UK, was in the O’Keefe lab from 1996-2005, from his Master’s degree through postdoctoral work. In his own research today, he uses the in vivo techniques for recording brain signals from individual cells that he learned from O’Keefe. “The history of neuroscience is often the history of technical improvements,” says Lever, and that can also apply to the neuroscience-related industry.

The methods that were fundamental to O’Keefe’s Nobel Prize-winning work, says Lever, could benefit neurological drug development. For example, researchers developing a pro-cognitive drug might test it by seeing if it improves a mouse’s ability to find a hidden platform in an opaque pool of water (the Morris water maze assay). Adding targeted brain recordings could determine if any improved performance was because the drug improved spatial signaling or because it had other effects such as reducing anxiety, which might not help dementia.

O’Keefe encourages thinking about the big picture, says Lever. “He’s interested in fundamental questions, not incremental science.” The O’Keefe group has a relaxed, low-pressure atmosphere, says Lever. “It was possibly the most fun I’ve ever had in a lab.” His former mentor encourages thinking hard as well as working hard, says Lever. Making good use of time is a priority, as we know from stories about how O’Keefe heard about the Nobel honor. His routine is to work from home in the morning where he has fewer distractions and can be more efficient. He learned about the Nobel announcement when a colleague phoned to tell him that someone from Sweden was trying to contact him “and said it was urgent.”

Exploring next door

O’Keefe continues to study the hippocampus and spatial cognition. In addition, he is applying the same open-ended, exploratory approach that revealed the spatial functions of the hippocampus to a new brain area: the amygdala. “I’m trying to do with the amygdala what I did with the hippocampus,” says O’Keefe: “Go in and just see what cells are interesting.” The amygdala seems like a rich area for new discoveries, says O’Keefe, because it is involved in memory and emotion and cognition about important items in an animal’s environment such as food and other animals. It’s a natural next step for O’Keefe because, he says, “It sits next to the hippocampus and they talk to each other.”

O’Keefe expected to be busy every minute during the Nobel week with scheduled events. His wife, their two sons and their wives joined him on the trip to Stockholm. When they return to London, says O’Keefe, he is looking forward to getting back to work, including bench work. “Obviously, I have students who do a lot of it,” he says, “but I sneak into lab in the evening when things quiet down a bit and I do some research myself. That’s where I really get my kicks.”

 

Info Box

John O’Keefe

Born: 1949, New York, USA

Educated: City College of New York and McGill University, Montreal

Career: Postdoctoral fellow and professor at University College London; currently director of the Sainsbury Wellcome Centre in Neural Circuits and Behaviour, University College London

Family: Married to Public Health Professor Eileen O’Keefe; two adult sons