John O'Keefe (neuroscientist)

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John O'Keefe

John O'Keefe (neuroscientist) 2014 (cropped).jpg
John O'Keefe in September 2014
Born (1939-11-18) November 18, 1939 (age 80)
CitizenshipUnited Kingdom, United States
Alma mater City College of New York
McGill University
Known forDiscovering place cells
Awards Nobel Prize in Physiology or Medicine (2014)
Kavli Prize (2014)
Physiological Society Annual Review Prize Lecture (2016)
Scientific career
Fields Neuroscience
Institutions University College London
Thesis Response properties of amygdalar units in the freely moving cat  (1967)
Doctoral advisor Ronald Melzack
Notable students Neil Burgess (postdoc) [1]
Website Website at UCL

John O'Keefe, FRS FMedSci (born November 18, 1939) is an American-British neuroscientist 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.

Contents

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

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

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 Dr. John O' Keefe, Nobel laureate in Medicine.jpg
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]

Related Research Articles

Entorhinal cortex Part of the brains cerebral cortex

The entorhinal cortex (EC) is an area of the brain located in the medial temporal lobe and functions as a hub in a widespread network for memory, navigation and the perception of time. The EC is the main interface between the hippocampus and neocortex. The EC-hippocampus system plays an important role in declarative (autobiographical/episodic/semantic) memories and in particular spatial memories including memory formation, memory consolidation, and memory optimization in sleep. The EC is also responsible for the pre-processing (familiarity) of the input signals in the reflex nictitating membrane response of classical trace conditioning; the association of impulses from the eye and the ear occurs in the entorhinal cortex.

Hippocampus brain region correlated with memory consolidation and imagination

The hippocampus is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, and plays important roles in the consolidation of information from short-term memory to long-term memory, and in spatial memory that enables navigation. The hippocampus is located under the cerebral cortex in the allocortex, and in primates it is in the medial temporal lobe. It contains two main interlocking parts: the hippocampus proper and the dentate gyrus.

Dentate gyrus Part of a brain region known as the hippocampus which is part of the hippocampal formation

The dentate gyrus (DG) is part of the hippocampal formation in the temporal lobe of the brain that includes the hippocampus and the subiculum. The dentate gyrus is part of the hippocampal trisynaptic circuit and is thought to contribute to the formation of new episodic memories, the spontaneous exploration of novel environments and other functions.

Place cell Hippocampal cell that plays a role in localization

A place cell is a kind of pyramidal neuron within the hippocampus that becomes active when an animal enters a particular place in its environment, which is known as the place field. Place cells are thought, collectively, to act as a cognitive representation of a specific location in space, known as a cognitive map. Place cells work with other types of neurons in the hippocampus and surrounding regions to perform this kind of spatial processing. They have been found in a variety of animals, including rodents, bats, monkeys and humans.

Susumu Tonegawa Japanese biologist

Susumu Tonegawa is a Japanese scientist who was the sole recipient of the Nobel Prize for Physiology or Medicine in 1987, for his discovery of the genetic mechanism that produces antibody diversity. Although he won the Nobel Prize for his work in immunology, Tonegawa is a molecular biologist by training and he again changed fields following his Nobel Prize win; he now studies neuroscience, examining the molecular, cellular and neuronal basis of memory formation and retrieval.

Cognitive map type of mental representation

A cognitive map is a type of mental representation which serves an individual to acquire, code, store, recall, and decode information about the relative locations and attributes of phenomena in their everyday or metaphorical spatial environment. The concept was introduced by Edward Tolman in 1948. The concept was used to explain the behavior of rats that appeared to learn the spatial layout of a maze, and subsequently the concept was applied to other animals, including humans. The term was later generalized by some researchers, especially in the field of operations research, to refer to a kind of semantic network representing an individual's personal knowledge or schemas.

Subiculum

The subiculum is the most inferior component of the hippocampal formation. It lies between the entorhinal cortex and the CA1 subfield of the hippocampus proper.

Hippocampal formation A compound structure in the medial temporal lobe of the brain

The hippocampal formation is a compound structure in the medial temporal lobe of the brain. There is no consensus concerning which brain regions are encompassed by the term, with some authors defining it as the dentate gyrus, the hippocampus proper and the subiculum; and others including also the presubiculum, parasubiculum, and entorhinal cortex. The hippocampal formation is thought to play a role in memory, spatial navigation and control of attention. The neural layout and pathways within the hippocampal formation are very similar in all mammals.

Grid cell type of neuron

A grid cell is a type of neuron within the entorhinal cortex that fires at regular intervals as an animal navigates an open area, allowing it to understand its position in space by storing and integrating information about location, distance, and direction. Grid cells have been found in many animals, including rats, mice, bats, monkeys, and humans.

Moser research environment neuroscience research center at the Norwegian University of Science and Technology (NTNU)

The Moser research environment is the informal name of Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology (NTNU) in Trondheim, Norway. The neuroscience research institute is founded and led by the Nobel laureates Edvard Moser and May-Britt Moser since 1996. The Kavli Institute for Systems Neuroscience comprises two research centres: Centre for Neural Computation (CNC), a centre of excellence since 2002; and the Egil and Pauline Braathen and Fred Kavli Centre for Cortical Microcircuits (BKC).

Boundary cell

Boundary cells are neurons found in the hippocampal formation that respond to the presence of an environmental boundary at a particular distance and direction from an animal. The existence of cells with these firing characteristics were first predicted on the basis of properties of place cells. Boundary cells were subsequently discovered in several regions of the hippocampal formation: the subiculum, presubiculum and entorhinal cortex.

Edvard Moser Norwegian psychologist and neuroscientist

Edvard Ingjald Moser is a Norwegian professor of psychology and neuroscience at the Kavli Institute for Systems Neuroscience, at the Norwegian University of Science and Technology (NTNU) in Trondheim. In 2005 he discovered grid cells in the brain's medial entorhinal cortex. Grid cells are specialized neurons that provide the brain with a coordinate system and a metric for space. In 2018 he discovered a neural network that expresses your sense of time in experiences and memories located in the brain's lateral entorhinal cortex He shared the Nobel Prize in Physiology or Medicine in 2014 with long-term collaborator May-Britt Moser and previous mentor John O'Keefe for their work identifying the brain's positioning system. The two main components of the brain's GPS are; grid cells and place cells, a specialized type of neuron that respond to specific locations in space. Together with May-Britt Moser he established the Moser research environment, which they lead.

May-Britt Moser Norwegian psychologist and neuroscientist

May-Britt Moser is a Norwegian psychologist and neuroscientist, who is a Professor of Psychology and Neuroscience at the Norwegian University of Science and Technology (NTNU). She and her then-husband, Edvard Moser, shared half of the 2014 Nobel Prize in Physiology or Medicine, awarded for work concerning the grid cells in the entorhinal cortex, as well as several additional space-representing cell types in the same circuit that make up the positioning system in the brain. Together with Edvard Moser she established the Moser research environment at NTNU, which they lead. Since 2012 she heads the Centre for Neural Computation.

Medial septal nucleus

The medial septal nucleus (MS) is one of the septal nuclei. Neurons in this nucleus give rise to the bulk of efferents from the septal nuclei. A major projection from the medial septal nucleus terminates in the hippocampal formation.

James B. Ranck Jr. is a distinguished professor of Physiology at the SUNY Downstate Medical Center. His research involves recording from single neurons in living animals for behavioral studies. He discovered head-direction cells in 1984.

Sharp waves and ripples (SWRs) are oscillatory patterns in the mammalian brain hippocampus seen on an EEG during immobility and sleep. There are three major network oscillation patterns in the hippocampus: theta waves, SWRs and gamma waves. Gamma oscillations are found in all major brain structures, whereas theta and sharp waves are specific to the hippocampus and its neighbouring areas. SWRs are composed of large amplitude sharp waves in local field potential and associated fast field oscillations known as ripples. SWRs are shown to be involved in memory consolidation and the replay of wakefulness-acquired memory. These network oscillations are the most synchronous patterns in the brain, making them susceptible to pathological patterns such as epilepsy.

Phase resetting in neurons

Phase resetting in neurons is a behavior observed in different biological oscillators and plays a role in creating neural synchronization as well as different processes within the body. Phase resetting in neurons is when the dynamical behavior of an oscillation is shifted. This occurs when a stimulus perturbs the phase within an oscillatory cycle and a change in period occurs. The periods of these oscillations can vary depending on the biological system, with examples such as: (1) neural responses can change within a millisecond to quickly relay information; (2) In cardiac and respiratory changes that occur throughout the day, could be within seconds; (3) circadian rhythms may vary throughout a series of days; (4) rhythms such as hibernation may have periods that are measured in years. This activity pattern of neurons is a phenomenon seen in various neural circuits throughout the body and is seen in single neuron models and within clusters of neurons. Many of these models utilize phase response (resetting) curves where the oscillation of a neuron is perturbed and the effect the perturbation has on the phase cycle of a neuron is measured.

The Perl-UNC Prize is awarded internationally in the field of neuroscience. Its purpose is two-fold: to recognize researchers for outstanding discoveries and seminal insights in neuroscience and to celebrate the strength of the neuroscience research program at the University of North Carolina at Chapel Hill. As of 2017, six recipients of the Perl-UNC Prize have gone on to win Nobel Prizes; an additional three have won Kavli Prizes in Neuroscience.

Attila Losonczy is a Hungarian neuroscientist, Professor of Neuroscience at Columbia University Medical Center. Losonczy's main area of research is on the relationship between neural networks and behavior, specifically with regard to learning in the hippocampus.

Phase precession

Phase precession is a neurophysiological process in which the firing of action potentials by individual neurons is timed in relation to the phase of neural oscillations in the surrounding cells. In place cells, a type of neuron found in the hippocampal region of the brain, phase precession is believed to play a major role in the neural coding of information. John O'Keefe, who later shared the 2014 Nobel Prize in Physiology or Medicine for his discovery that place cells help form a "map" of the body's position in space, co-discovered phase precession with Michael Recce in 1993.

References

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