PubMed Health⌕ Search

Biomedical subjects

J O'Keefe

Publications and source records attributed to J O'Keefe.

13 recordsLinked to original sources
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↗
PubMed1978

Hippocampal place units in the freely moving rat: why they fire where they fire.

Place units in the dorsal hippocampus of the freely-moving rat signal the animal's position in an environment (place field). In the present experiments, thirty four place units were recorded in two different environments: one, a small platform where the rat had received neither training nor reward; the other, an elevated T-maze inside a set of black curtains where the rat had been trained on a place discrimination. The places within the curtained enclosure were specified by four cues (a light, a card, a fan, and a buzzer) in addition to the food. Other cues were eliminated by rotating the maze and the four controlled cues relative to the external world from trial-to-trial. Some units had place fields in both environments while others only had a place field in one. No relationship could be seen between the place fields of units with fields in both environments. All twelve units tested extensively in the controlled enclosure had place fields related to the controlled cues. Probe experiments in which only some of the controlled cues were available showed that some of these units were being excited by one or two cues while others were influenced in a more complex way. The fields of these latter units were maintained by any two of the 4 cues and were due to inhibitory influences which suppressed the unit firing over the rest of the maze.

Acoustic Stimulation↗
PubMed1977

Single unit and lesion experiments on the sensory inputs to the hippocampal cognitive map.

The hippocampal cognitive map theory states that the hippocampus calculates the animal's location in an environment and also the locations of objects such as rewards and threats. In this paper we report single cell experiments which explored how sensory inputs are used by the hippocampus to calculate spatial information and behavioural experiments which tested the sensory capabilities of fornix-lesioned rats. Both sets of experiments were done in cue-controlled enclosures which contained only a few distant cues by which the rat could locate itself and the goal. Other cues were eliminated by rotating the constellation of cues and the goal from trial to trial. The results of the single cell experiment show that the place fields of hippocampal cells recorded in this environment are related to the controlled cues and, further, that some of these place cells maintain their fields after the removal of any two of four controlled cues. The lesion studies show that rats with damaged fornices can learn to approach distant cues behind and below the level of the goal but not ones behind and above the goal. A second study showed that the addition of redundant distant cues to the enclosure impairs the learning ability of the lesioned, but not the normal, animals.

Animals↗