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CDB Seminars
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All Seminars are held in the Gavin De Beer Lecture Theatre, Anatomy Building, Thursday 1-2pm

11 Dec: Marcus Ghosh (Rihel lab)/ (Chubbs lab)

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OVERVIEW: SPACE, MEMORY, AND THE HIPPOCAMPUS


John O'Keefe, PhD, FRS
Group leader
Contact: John O'Keefe

How do animals and humans remember important places in their environments, and find their way back to them again? A critical structure is the hippocampus, which also supports episodic memory (memory for events: things that happened in a particular place and time). Hippocampal degeneration is the most dramatic feature of Alzheimer's disease, in which spatial disorientation and amnesia are early and devastating symptoms.

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The hippocampus of the human   brain

The work of my lab aims to understand the neuronal basis of spatial memory formation. I have found neurons in the hippocampus of rats that fire most strongly when the rat is in a particular part of its environment. The question then arises as to how a given place cell "knows" where the rat is. Recently, we have found that the cells respond to the distance of the rat from the walls of the environment, each cell preferring different combinations of walls. The cells use a mixture of visual features and information about the animal's movements to identify how far the rat is from a given wall, and to discriminate identical walls. In collaboration with Neil Burgess, we have used the known properties of place cells to create a computer model of navigation, which is able to guide a "robotic rat" to locations in its environment.  

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(Left) Rat hippocampus (Right) Firing of 4 place cells in a square box

Functional imaging techniques such as PET and fMRI can enable studies of spatial behaviour in humans. In collaboration with colleagues at the FIL, Queens Square, we have found that the hippocampus and adjacent parahippocampal cortex become most active when the subjects navigate through a virtual reality environment, or imagine navigating through a real one. Thus, it appears that the spatial function of the hippocampus is probably common to all mammals. Finding out how spatial memory is stored is the next step: this will enable us to understand better why patients with hippocampal damage are so profoundly amnesic, and perhaps to develop treatments.

Selected Recent Papers:

C Lever, T Wills, F Cacucci, N Burgess, J O'Keefe (2002) Long-term plasticity in the hippocampal representation of environmental geometry. Nature 416: 90-94

Burton S, Murphy D, Qureshi U, Sutton P, O'Keefe J (2000) Combined lesions of hippocampus and subiculum do not produce deficits in a nonspatial social olfactory memory task. J Neurosci 20: 5468-75

KJ Jeffery and JM O'Keefe (1999) Learned interaction of visual and idiothetic cues in the control of place field orientation. Exp. Brain Res. 127: 151-161

J. O'Keefe and N. Burgess (1999) Theta activity, virtual navigation and the human hippocampus. Trends in Cognitive Science 3 403-406.

Burgess, N., Jeffery, K.J. and O'Keefe, J. (Eds) (1999) The Hippocampal and Parietal Foundations of Spatial Cognition. Oxford University Press

Maguire E.,A. Burgess, N., Donnett, J.G., Frackowiak,R.S.J., Frith, C.D. and O'Keefe, J. (1998) Knowing where, and getting there: a human navigation network. Science 280: 921-924. J O'Keefe, N Burgess, JG Donnett, KJ Jeffery, EA Maguire (1998) Place cells, navigational accuracy, and the human hippocampus. Philos Trans R Soc Lond B Biol Sci. 353(1373):1333-40.

KJ Jeffery, JG Donnett, N Burgess, J O'Keefe (1997) Directional control of hippocampal place fields. Exp. Brain Res. 117 131-142.

O'Keefe J. and Burgess N. (1996) Geometric determinants of the place fields of hippocampal neurons. Nature 381: 425-428.

Books:

Burgess, N., Jeffery, K.J. and O'Keefe, J. (Eds) (1999) The Hippocampal and Parietal Foundations of Spatial Cognition. Oxford University Press

O'Keefe, J and Nadel, L (1978) The Hippocampus as a cognitive map. Oxford University Press
To download, at no cost, part or all of this book (pdf), go to the cognitivemap.net website.

Neil Burgess, PhD
Group leader
Contact: Neil Burgess
HomePage

Current research:

I use computational models to examine the role of place cell firing in providing a memory for unmarked goal locations that could enable the rat to return to them. A mobile robot is used to test the model's ability to navigate using real-world inputs, and to generate behavioural data. The models suggests functional constraints on the inputs to place cells, which are tested and revised in experiments performed with John O'Keefe's group (this department). These have led to a good appreciation of which aspects of an environment determine a rat's representation of its own location. Computational modelling has also suggested how information could be encoded in the timing of the firing of place cells, and how this information might be used.

In humans, the hippocampus has traditionally been associated with a more general role in providing memory for personally experienced events. How can this be squared with its spatial role in rats? Using a modified video game, I have developed a complex virtual reality environment in which to test the spatial abilities of human subjects. With John O'Keefe, Eleanor Maguire and Chris Frith (Wellcome Institute of Cognitive Neurology) we have used this with functional neuroimaging to investigate which parts of the human brain are activated in the performance of spatial navigation. Our results associate activation of the right hippocampus and right inferior parietal cortex correlates with the accuracy of navigation, while activation of the right caudate correlates with the speed of navigation. We are currently devising a series of related spatial and mnemonic tests for patients with selective hippocampal pathology, in collaboration with Faraneh Vargha-Khadem (Inst. of Child Health), David Fish (National Hospital of Neurology) and Pam Thomson (National Society for Epilepsy).

How does the brain represent and store the temporal order of events? Psychological experiments have provided strong constraints on mechanisms underlying short-term memory for the order of verbal items. With Graham Hitch (Lancaster University) I have developed a neural network model of this type of memory. We are currently testing the predictions of this model in a series of psychological and functional neuroimaging experiments. The development of a coherent model of the functional roles of hippocampal and parietal areas in long- and short-term memory for spatial, verbal and episodic memory remains an exciting, if remote, target for my research.

Selected Publications:

Burgess N., Maguire E.A., O'Keefe J. (2002) The human hippocampus and spatial and episodic memory. Neuron 35 625-641.

Burgess N., Becker S., King J.A., O'Keefe J. (2001) Memory for events and their spatial context: models and experiments. Philos.Trans.R.Soc.Lond B 356 1493-1503.

Burgess N., Maguire E.A., Spiers H.J., O'Keefe J. (2001) A temporoparietal and prefrontal network for retrieving the spatial context of lifelike events. NeuroImage 14 439-453.

N Burgess, KJ Jeffery, J O'Keefe (Eds.) (1999)The Hippocampal and Parietal Foundations of Spatial Cognition UK: Oxford University Press

Maguire EA, Burgess N, Donnett JG, Frith CD, Frackowiak RSJ, O'Keefe J (1998). Knowing where and getting there: a human navigation system. Science, 280 921-924.

Burgess N, Donnett JG, Jeffery KJ, O'Keefe J (1997). Robotic and neuronal simulation of the hippocampus and rat navigation. Phil. Trans. Roy. Soc. B 352 1535-1543.

Burgess N, Hitch GJ (1992). Toward a Network Model of the Articulatory Loop. J. Memory & Language 31 429-460.

Click here for a more comprehensive Publication List

Page last modified on 03 jun 10 11:32 by Glenda Young