John O'Keefe (neuroscientist)

John O'Keefe, FRS FMedSci (born November 18, 1939) is an American-British neuroscientist, psychologist and a professor at the Sainsbury Wellcome Centre for Neural Circuits and Behaviour and the Research Department of Cell and Developmental Biology at University College London. He discovered place cells in the hippocampus, and that they show a specific kind of temporal coding in the form of theta phase precession. He shared the Nobel Prize in Physiology or Medicine in 2014, together with May-Britt Moser and Edvard Moser; he has received several other awards. He has worked at the University College London for his entire career, but also held a part-time chair at the Norwegian University of Science and Technology at the behest of his Norwegian collaborators, the Mosers.

John O'Keefe

FRS FMedSci
John O'Keefe in September 2014
Born (1939-11-18) November 18, 1939
New York City, New York
CitizenshipUnited Kingdom, United States
Alma materCity College of New York
McGill University
Known forDiscovering place cells
AwardsNobel Prize in Physiology or Medicine (2014)
Kavli Prize (2014)
Physiological Society Annual Review Prize Lecture (2016)
Scientific career
FieldsNeuroscience, Psychology
InstitutionsUniversity College London
ThesisResponse properties of amygdalar units in the freely moving cat (1967)
Doctoral advisorRonald Melzack
Notable studentsNeil Burgess (postdoc)[1]
WebsiteWebsite at UCL

Education and early life

Born in New York City to Irish immigrant parents, O'Keefe attended Regis High School (Manhattan) and received a BA degree from the City College of New York.[2][3] He went on to study at McGill University in Montreal, Quebec, Canada, where he obtained an MA degree in 1964, and a PhD degree in Psychology in 1967, supervised by Ronald Melzack.[4][5][6]

Career and research

O'Keefe went to University College London in 1967 as a US NIMH postdoctoral research fellow working with the late Patrick Wall. He has been there ever since and was promoted to Professor in 1987. At the behest of his collaborators Edvard Moser and May-Britt Moser he was appointed to a part-time professorial chair at the Norwegian University of Science and Technology in 2014.[7]

Discovery of place cells
See also: Place cell

O’Keefe and his student Jonathan Dostrovsky discovered place cells by systematically analyzing the environmental factors influencing the firing properties of individual hippocampal neurons.[8][9] His many publications on place cells have been highly cited. In addition, he published an influential book with Lynn Nadel, proposing the functional role of the hippocampus as a cognitive map for spatial memory function.[10] In extensions of his work, place cells have been analyzed experimentally or simulated in models in hundreds of papers.[11][12][13]

Discovery of theta phase precession

In further research on place cells, O’Keefe found evidence for a distinctive variation of temporal coding of information by the timing of action potentials in place cells, relative to an oscillatory EEG cycle known as the theta rhythm, as opposed to spike timing within a single cell. In a 1993 paper, he and Michael Recce demonstrated that place cells spike at different phases relative to theta rhythm oscillations in the local field potential of the hippocampus.[14] As a rat enters the firing field of a place cell, the spiking starts at late phases of theta rhythm, and as the rat moves through the firing field, the spikes shift to earlier phases of the theta cycle. This effect has been replicated in numerous subsequent papers, providing evidence for the coding of sensory input by the timing of spikes. Numerous models have addressed the potential physiological mechanisms of theta phase precession.

Prediction and discovery of boundary vector cells
See also: Boundary cell

In a paper in 1996, O'Keefe and Neil Burgess presented data showing shifts in the position and size of place cell firing fields when the barriers defining the environment were shifted.[1] In this and subsequent papers, they presented a model of this phenomenon predicting the existence of boundary vector cells that would respond at a specific distance from barriers in the environment.[15] Several years later, this explicit theoretical prediction was supported by extensive experimental data demonstrating boundary cells with the predicted properties in the subiculum[16] and the medial entorhinal cortex (where they are sometimes referred to as border cells).

Awards and honours
O'Keefe giving Nobel lecture in Oslo, December 2014

O'Keefe was elected a Fellow of the Royal Society (FRS) in 1992 and a Fellow of the Academy of Medical Sciences (FMedSci) in 1998. In addition, he received the Feldberg Foundation Prize in 2001 and the Grawemeyer Award in psychology in 2006 (with Lynn Nadel). In 2007, he received the British Neuroscience Association Award for Outstanding Contribution to British Neuroscience and in 2008 he received the Federation of European Neuroscience Societies European Journal of Neuroscience Award. Later in 2008, O'Keefe was awarded the Gruber Prize in Neuroscience.[17][18] He was appointed as the inaugural director of the Sainsbury Wellcome Centre for Neural Circuits and Behaviour.[19] In 2013 he received the Louisa Gross Horwitz Prize (with Edvard Moser and May-Britt Moser).[20] In 2014, he was a co-recipient of the Kavli Prize awarded by the Norwegian Academy of Science and Letters with Brenda Milner and Marcus Raichle.[21] In 2016 he was elected to the National Academy of Sciences.[22]

O'Keefe was awarded the Nobel Prize in Physiology or Medicine 2014, with May-Britt Moser and Edvard Moser.[23]

O'Keefe received an honorary Doctor of Science degree from University College Cork on 15 December 2014.[24] In May 2015, he received one from The City College of New York,[25] and in June of the same year, he was awarded one from McGill University, both his alma maters.[26]

In 2014 he received the Kavli Prize in Neuroscience "for the discovery of specialized brain networks for memory and cognition", together with Brenda Milner and Marcus Raichle.

On 10 March 2015, O'Keefe was the guest on BBC Radio 4's The Life Scientific.[27]

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References
  1. O'Keefe, J.; Burgess, N. (1996). "Geometric determinants of the place fields of hippocampal neurons". Nature. 381 (6581): 425–428. Bibcode:1996Natur.381..425O. doi:10.1038/381425a0. PMID 8632799.
  2. "2008 Neuroscience Prize. John O'Keefe". Gruber Foundation. Retrieved 2013-11-23.
  3. "John O'Keefe, Class of '63, Wins Nobel Prize". The City College of New York. 6 October 2014. Retrieved 8 October 2014.
  4. "John O'Keefe". Kavli Prize. Kavli Foundation. Retrieved 11 October 2014.
  5. "McGill grad John O'Keefe wins Nobel Prize in medicine". Media Relations Office of McGill University. 6 October 2014. Retrieved 8 October 2014.
  6. O'Keefe, John (1967). Response properties of amygdalar units in the freely moving cat (Ph.D.). Montreal, Quebec, Canada: McGill University. OCLC 894987156.
  7. "NTNU ansetter nobelprisvinner O'Keefe". 2014-12-08.
  8. O'Keefe, J.; Dostrovsky, J. (1971). "The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat". Brain Research. 34 (1): 171–175. doi:10.1016/0006-8993(71)90358-1. PMID 5124915.
  9. O'Keefe, J (1976). "Place units in the hippocampus of the freely moving rat". Experimental Neurology. 51 (1): 78–109. doi:10.1016/0014-4886(76)90055-8. PMID 1261644.
  10. O'Keefe, J.; Nadel, L. (1978). The Hippocampus as a Cognitive Map. Oxford, United Kingdom: Oxford University Press.
  11. O'Keefe, J (1979). "A review of the hippocampal place cells". Progress in Neurobiology. 13 (4): 419–39. doi:10.1016/0301-0082(79)90005-4. PMID 396576.
  12. Best, P. J.; White, A. M.; Minai, A (2001). "Spatial processing in the brain: The activity of hippocampal place cells". Annual Review of Neuroscience. 24: 459–86. doi:10.1146/annurev.neuro.24.1.459. PMID 11283318.
  13. Moser, E.; Kropff, E.; Moser, M. (2008). "Place cells, grid cells, and the brain's spatial representation system". Annual Review of Neuroscience. 31: 69–89. doi:10.1146/annurev.neuro.31.061307.090723. ISSN 0147-006X. PMID 18284371.
  14. O'Keefe, J; Recce, M. L. (1993). "Phase relationship between hippocampal place units and the EEG theta rhythm". Hippocampus. 3 (3): 317–30. doi:10.1002/hipo.450030307. PMID 8353611.
  15. Hartley, Tom; Burgess, N.; Lever, C.; Cacucci, F.; O'Keefe, J. (2000). "Modeling place fields in terms of the cortical inputs to the hippocampus". Hippocampus. 10 (4): 369–379. CiteSeerX 10.1.1.19.7928. doi:10.1002/1098-1063(2000)10:4<369::AID-HIPO3>3.0.CO;2-0. ISSN 1050-9631. PMID 10985276.
  16. Lever, C.; Burton, S.; Jeewajee, A.; O'Keefe, J.; Burgess, N. (2009). "Boundary Vector Cells in the Subiculum of the Hippocampal Formation". Journal of Neuroscience. 29 (31): 9771–9777. doi:10.1523/JNEUROSCI.1319-09.2009. PMC 2736390. PMID 19657030.
  17. "UCL neuroscientist receives international prize for 'pioneering work'". Ucl.ac.uk. 2008-06-23. Retrieved 2013-11-23.
  18. "2008 Neuroscience Prize. John O'Keefe. Laureate Profile". Gruber Foundation. Retrieved 2013-11-23.
  19. "Sainsbury Wellcome Centre for Neural Circuits and Behaviour". Gatsby. Retrieved 2013-11-23.
  20. Louisa Gross Horwitz Prize 2013. cumc.columbia.edu
  21. Bhattacharjee, Yudhijit (29 May 2014). "Nine Scientists Share Three Kavli Prizes". news.sciencemag.org.
  22. National Academy of Sciences Members and Foreign Associates Elected, News from the National Academy of Sciences, National Academy of Sciences, May 3, 2016, archived from the original on May 6, 2016, retrieved 2016-05-14.
  23. "The Nobel Prize in Physiology or Medicine 2014". www.nobelprize.org.
  24. Roche, Barry, "UCC to honour Nobel Laureate", The Irish Times, 7 October 2014
  25. Admin, Website (25 July 2015). "CCNY Names Top Three for 2015 Commencement Honors - The City College of New York". www.ccny.cuny.edu.
  26. "McGill to award 16 honorary degrees : McGill Reporter". publications.mcgill.ca.
  27. "John O'Keefe on memory, The Life Scientific - BBC Radio 4". BBC.
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