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J O'Keefe

Publications and source records attributed to J O'Keefe.

At least 73 records · Page 4Linked to original sources
PubMed1993

Hippocampus, theta, and spatial memory.

The past 18 months have witnessed interesting developments in several areas of hippocampal research. First, the mechanisms of hippocampal theta are becoming clear, as is its role in spatial coding; each theta cycle appears to act as a clock mechanism against which the firing of the place cells can be timed. Second, there has been a continued strengthening in the support for the spatial theory of hippocampal function from single unit and lesion experiments; particularly important is the finding that the deficit in (non-spatial) delayed non-match to sample memory experiments in the monkey following medial temporal lobe damage stems from the part of the cortex which surrounds the hippocampus, and not from the hippocampus itself. Third, in contrast, it is proving more difficult than originally thought to show a causal relationship between long-term potentiation at the synaptic level and place learning-induced changes in hippocampal synapses.

Animals↗
PubMed1992

Thrombin receptor expression in normal and atherosclerotic human arteries.

Thrombin is a multifunctional serine protease generated at sites of vascular injury. A host of thrombin actions on vascular endothelial cells, smooth muscle cells, and macrophages has been defined in cell culture systems, but the in vivo significance of these activities is unknown. We have defined the expression of the recently identified receptor for thrombin in human arteries by both in situ hybridization and immunohistochemistry. In normal-appearing arteries, thrombin receptor was expressed almost exclusively in the endothelial layer. By contrast, in human atheroma, the receptor was widely expressed, both in regions rich in macrophages and in regions rich in vascular smooth muscle cells and mesenchymal-appearing intimal cells of unknown origin. Thrombin receptor was expressed by human vascular endothelial cells and smooth muscle cells in culture and by macrophages obtained by bronchioalveolar lavage, thus demonstrating that all three cell types are indeed capable of expressing the thrombin receptor. These results establish thrombin receptor activation as a candidate for contributing to sclerotic and inflammatory processes in the human vasculature, such as those that occur in atherosclerosis and restenosis.

Arteries↗
PubMed1990

A computational theory of the hippocampal cognitive map.

Evidence from single unit and lesion studies suggests that the hippocampal formation acts as a spatial or cognitive map (O'Keefe and Nadel, 1978). In this chapter, I summarise some of the unit recording data and then outline the most recent computational version of the cognitive map theory. The novel aspects of the present version of the theory are that it identifies two allocentric parameters, the centroid and the eccentricity, which can be calculated from the array of cues in an environment and which can serve as the bases for an allocentric polar co-ordinate system. Computations within this framework enable the animal to identify its location within an environment, to predict the location which will be reached as a result of any specific movement from that location, and conversely, to calculate the spatial transformation necessary to go from the current location to a desired location. Aspects of the model are identified with the information provided by cells in the hippocampus and dorsal presubiculum. The hippocampal place cells are involved in the calculation of the centroid and the presubicular direction cells in the calculation of the eccentricity.

Animals↗
PubMed1987

Single unit activity in the rat hippocampus during a spatial memory task.

Single unit activity was recorded from complex spike cells in the hippocampus of the rat while the animal was performing a spatial memory task. The task required the animal to choose the correct arm of a 4 arm plus-shaped maze in order to obtain reward. The location of the goal arm was varied from trial to trial and was identified by 6 controlled spatial cues which were distributed around the enclosure and which were rotated in step with the goal. On some trials these spatial cues were present throughout the trial (spatial reference memory trials) while on other trials they were present during the first part of the trial but were removed before the rat was allowed to choose the goal (spatial working memory trials). On these latter trials the animal had to remember the location of the cues and/or goal during the delay in order to choose correctly. 55 units were recorded during sufficient reference memory trials for the relationship between their firing pattern and different spatial aspects of the environment to be determined. 33 units had fields with significant relations to the controlled cues while 16 had significant relations to the static background cues, those cues in the environment which did not change position from trial to trial. Of 43 units which could be tested for their relation to the shape of the maze arms themselves, 15 showed such a relationship. Therefore the place units can be influenced by different aspects of the spatial environment but those related to the task requirement appear to be more potent. Interaction effects between the different spatial factors also influenced the firing pattern of some units. Of particular interest was the interaction between the controlled cues and the static background cues found in some cells since this might shed some light on how the hippocampus enables the rat to solve the memory task. 30 units with place fields related to the controlled cues were recorded during successful performance on spatial working memory trials as well as during spatial reference memory trials. The place fields of 90% of these units were maintained during the retention phase of the memory trials. During the recording of some units, other types of trial were given as well. On control trials, the cues were removed before the rat was placed on the maze. These trials provided controls for the potential influence of information left behind by the controlled cues and for the influence of the animal's behaviour on the unit activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Management of ventricular arrhythmias associated with mitral valve prolapse by combined alpha and beta blockade.

Ventricular arrhythmias are common in patients with mitral valve prolapse. Ten patients with echocardiographically confirmed mitral valve prolapse and documented ventricular arrhythmias were included in this study. The aim was to assess the value of combined alpha- and beta-blockade (labetalol) compared with beta-blockade alone (propranolol) in the management of ventricular arrhythmias in these patients. The study was performed using physiological stress, such as the Valsalva manoeuvre, isometric exercise and treadmill exercise, to initiate ventricular arrhythmias before and after intravenous propranolol or labetalol and to document arrhythmias during 24 hour electrocardiography before and after oral medication. Labetalol and propranolol decreased the heart rate and blood pressure response to these manoeuvres to a similar extent but labetalol was more effective in the control of the ventricular arrhythmias. These findings suggest that alpha adrenergic receptors may play a role in the pathogenesis of the ventricular arrhythmias in mitral valve prolapse syndrome and that labetalol offers an alternative treatment for the management of this condition.

Adult↗
PubMed1983

The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats.

Isolated single units in rat dorsal hippocampus and fascia dentata were classified as 'Theta' or 'Complex-Spike' cells, and their firing characteristics were examined with respect to position, direction and velocity of movement during forced choice, food rewarded search behavior on a radial eight arm maze. Most spikes from CS cells occurred when the animal was located within a particular place on the maze and moving in a particular direction. Theta cells had very low spatial selectivity. Both cell categories had discharge probabilities which increased somewhat as a function of running velocity but tended to asymptote well before half-maximal velocity. The place/direction specificity of CS cells was significantly higher in CA1 than in CA3 and CA3 CS cells exhibited a striking preference for the inward radial direction. The pronounced directional selectivity of CS cells, at least in the present environment, suggests that they fire in response to complex, but specific, stimulus features in the extramaze world rather than to absolute place in a non-egocentric space. An alternative possibility is that the geometrical constraints of the maze surface have a profound influence on the shapes of the response fields of CS cells.

Animals↗
PubMed1983

The stereotrode: a new technique for simultaneous isolation of several single units in the central nervous system from multiple unit records.

A new method is described for the recording and discrimination of extracellular action potentials in CNS regions with high cellular packing density or where there is intrinsic variation in action potential amplitude during burst discharge. The method is based on the principle that cells with different ratios of distances from two electrode tips will have different spike-amplitude ratios when recorded on two channels. The two channel amplitude ratio will remain constant regardless of intrinsic variation in the absolute amplitude of the signals. The method has been applied to the rat hippocampal formation, from which up to 5 units have been simultaneously isolated. The construction of the electrodes is simple, relatively fast, and reliable, and their low tip impedances result in excellent signal to noise characteristics.

Animals↗
PubMed1983

Loss of place specificity in hippocampal complex spike cells of senescent rat.

Firing characteristics of "place" cells in dorsal CA1 of hippocampus were recorded from 5 young (10-14 months) and 5 old (25-29 months) Fischer-344 rats. Animals were trained to obtain food reward on a radial 8-arm maze. Entry to the arms was controlled by the experimenter so that all 8-arm were visited in random sequence from trial to trial. For each cell, 8 such trials were given (64 arm choices) in order that statistical reliability could be obtained for firing rates over the maze surface. Single unit activity and the animal's position on the maze were continuously monitored by digital computer. Twenty-seven cells from each age group were studied in this way. No statistically significant differences were found between age groups in unit spike height, width or firing rates. A large, statistically significant difference, however, was found in both spatial specificity and reliability of firing patterns from trial to trial. These results are discussed in terms of a possible deficit in spatial information processing in the older animals.

Action Potentials↗
PubMed1980

Survival planning.

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Hospital Planning↗