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Biomedical subjects

C A Barnes

Publications and source records attributed to C A Barnes.

At least 109 records · Page 6Linked to original sources
PubMed1987

Increased electrotonic coupling in aged rat hippocampus: a possible mechanism for cellular excitability changes.

The effects of aging on the intercellular transfer of the low molecular weight fluorescent dye 5,6-carboxyfluorescein was studied in subfields fascia dentata, CA1, and CA3 of rat hippocampal slices maintained in vitro. All three areas exhibited a statistically significant increase in dye coupling with age. The increased dye coupling was accompanied by an apparent increase in postsynaptic excitability as assessed by the ratio of the population spike to EPSP components of the extracellulary recorded field potential. The possibility that artifactual dye coupling due to cell fusion contributed significantly to these results was ruled out by the demonstrations that a high molecular weight, dextran-coupled fluorescein compound did not produce multiple fills and that dye coupling with carboxyfluorescein could be prevented by prior intracellular loading with Ca++, a procedure that decouples gap junctions in other tissue. The increase in extent of electrical coupling suggested by these data may largely account for the apparent increase in cellular excitability of this tissue with age and may reflect the mechanism by which the senescent hippocampus compensates for the loss of afferent input during the course of normal aging. The additional possibility is raised that increased electrical coupling may reflect a mechanism for permanent associative storage of information in this system.

Aging↗
PubMed1987

Occlusion of hippocampal electrical junctions by intracellular calcium injection.

Low-molecular weight dyes such as Lucifer yellow or carboxyfluorescein have been used to investigate the electrical connectivity of neurons via gap junctions. The interpretation that such dye passage is mediated through intercellular channels has been controversial and difficult to corroborate with direct techniques in mammalian brain. We report here that elevated intracellular free Ca2+, a treatment shown to cause gap junction occlusion in other tissues, significantly blocks dye transfer between hippocampal cells. Furthermore, intracellular injection of FITC-dextran (which is too large to cross gap junctions) never resulted in multiple hippocampal cell fills. These data lend strong support to the argument that the extent of dye-coupling provides a good estimate of the number of intercellular communication channels, and raises the possibility that these channels may be physiologically modulated.

Animals↗
PubMed1987

Effects of aging on environmental modulation of hippocampal evoked responses.

Evoked responses in the dentate gyrus of the hippocampal formation undergo a long-term enhancement following high-frequency stimulation of the perforant pathway. A similar change results from exposure of animals to a complex spatial environment. The effect of aging on the development and decay of this environmentally induced response enhancement was examined in the present study. Previously it was shown that electrically induced enhancement reaches the same asymptotic level in young and old animals but decays more quickly in old animals. It has been suggested that this faster decay may underlie the faster forgetting of spatial information observed in old animals. Chronic recordings were made from young (14 month) and old (32 month) rats. After exposure to an enriched environment for 11 days, the population spike component of the response increased about 125% over baseline in both groups. No changes were seen in either group in the synaptic component. Following the enrichment treatment, animals were returned to their home cages. The decay of the enhanced population spike during this period differed markedly between age-groups (time constants of 30 and 11 days for the young and old groups, respectively). These results suggest that the factors governing the decay of electrically and environmentally induced response enhancement are similarly affected by the aging process and may share a common mechanism.

Afferent Pathways↗
PubMed1987

Production of heat shock protein is independent of cell cycle blockage in the yeast Saccharomyces cerevisiae.

In response to certain environmental stresses, cells display a response characterized by the production of heat shock proteins. In this study we showed that blockage of cells of the yeast Saccharomyces cerevisiae at specific points in the mitotic cell cycle was not in itself a stress that induced the production of heat shock proteins. Nevertheless, cell cycle blockage did not preclude a normal heat shock response in arrested cells subjected to elevated temperatures.

Cell Cycle↗
PubMed1986

Intracellular fluorescent staining with carboxyfluorescein: a rapid and reliable method for quantifying dye-coupling in mammalian central nervous system.

Previous studies investigating electrotonic coupling in mammalian central nervous system have used the fluorescent marker Lucifer Yellow as an indicator of the presence of intercellular junctions between neurons. The fluorescent dye 5,6-carboxyfluorescein is known to have approximately 5 times the fluorescent yield of Lucifer Yellow. We have investigated the use of this dye as a potential alternative fluorescent marker on two types of neurons in the rat hippocampus in vitro. Unfixed hippocampal slices were mounted in a mixture of n-propyl gallate in glycerol and viewed with epifluorescence optics. Injections of small, brief hyperpolarizing currents through carboxyfluorescein-filled glass pipettes reliably produced neuronal fills of good quality. Both dendritic spines and axonal arborizations (including the thin mossy fibers of the dentate gyrus) were frequently observable. In addition to single cell fills, clusters consisting of 2-6 neurons were observed. No correlation was found between the number of cells per cluster and the ejection time. In addition, even cells exhibiting poor electrophysiological characteristics, or cells impaled only briefly, frequently exhibited good quality dye filling. This method will be particularly useful when large sample sizes are necessary to compare regional variations in the extent of electrotonic coupling in the mammalian brain.

Animals↗
PubMed1986

Long-term enhancement of hippocampal synaptic transmission and the acquisition of spatial information.

The hypothesis that memories are stored as a specific distribution of strengths in a population of modifiable synapses was examined by the bilateral induction of long-term enhancement in synapses of the main afferent fiber system to the hippocampal formation in rats. Brief, high-frequency activation of the perforant pathway in chronically prepared animals resulted in a persistent increase in the field EPSP and population spike, measured extracellularly in fascia dentata. This treatment resulted in a profound and persistent deficit in the acquisition of new spatial information in a task requiring spatial "reference" memory, and disruption of recently acquired spatial information. Well-established spatial memory was completely unaffected, however, as was the acquisition of spatial information into short-term "working" memory. These results support the hypothesis that, during the formation of "cognitive maps," spatial information must be temporarily stored at modifiable synapses at the input stage to the hippocampal formation, but that this information is not needed once the representation of the environment is well established. Spatial working memory, in a familiar environment, appears not to depend on the distribution of synaptic strengths in this system at all.

Animals↗
PubMed1985

A selective increase in phosporylation of protein F1, a protein kinase C substrate, directly related to three day growth of long term synaptic enhancement.

Increased in vitro phosphorylation of the 47 kdalton, 4.5 pI protein F1 was observed in dorsal hippocampal tissue from animals exhibiting long term enhancement (LTE) three days after high frequency stimulation of the perforant pathway, as compared to tissue from low frequency stimulated controls or from unoperated animals. The increase in protein F1 phosphorylation was related to LTE rather than simple activation of perforant path-dentate gyrus synapses. This is the first report of a change in brain protein phosphorylation accompanying synaptic enhancement lasting days. The extent of growth of LTE over the three days following stimulation was directly related (r = +0.66, P less than 0.05) to protein F1 phosphorylation. Among the phosphoproteins studied this relationship between LTE and phosphorylation was selective for protein F1. This suggests that protein F1 may regulate growth of synaptic plasticity for at least a three day period. The mechanism for the LTE-related increase in protein F1 phosphorylation has not been established. However, recent evidence from this laboratory indicates: that protein F1 is phosphorylated by the calcium/phospholipid-dependent protein kinase C; and that kinase C is activated 1 h after LTE. Therefore, the increase in protein F1 phosphorylation following LTE may result from long term activation of protein C kinase.

Animals↗
PubMed1985

Enhancement of hippocampal field potentials in rats exposed to a novel, complex environment.

The hippocampus plays a crucial role in place learning in rodents and also exhibits a long-term enhancement of synaptic strength and postsynaptic excitability following electrical stimulation of its principal afferents. In the present report we suggest that these two observations may be related, by demonstrating an increase in synaptic and postsynaptic field potential amplitudes resulting from exposure to a spatially complex environment.

Animals↗
PubMed1985

An age comparison of the rates of acquisition and forgetting of spatial information in relation to long-term enhancement of hippocampal synapses.

Age differences in the rates of acquisition and forgetting of a spatial memory problem were compared with corresponding differences in the rates of increase and decay of long-term synaptic enhancement (LTE) of hippocampal synapses, induced by high-frequency stimulation of perforant path fibers. Old animals approached their final asymptotic performance levels more slowly than did the young animals and exhibited faster rates of forgetting of the problem. Similarly, LTE reached its maximum more slowly in the old animals and decayed more quickly. Although the absolute rates of behavioral acquisition and forgetting were different from the corresponding rates of increase and decay of LTE, the relative differences between age groups were rather similar. This was particularly true for the comparison of forgetting with LTE decay. The relation of these data to the hypothesis that LTE underlies spatial learning and memory is discussed.

Aging↗
PubMed1984

Disease staging: implications for hospital reimbursement and management.

The current patient classification schemes used in case-mix reimbursement are not fully sensitive to variations in resource consumption that are associated with differential disease severity. Disease staging is a clinically based measure of severity that uses objective medical criteria to assess the stage of disease progression. Its availability in automated form increases its ease of implementation in hospital reimbursement and management. Results of recent studies demonstrate that staging is a useful case-mix reimbursement and management tool that explains significant variation in cost per discharge within current diagnosis-related groups.

Costs and Cost Analysis↗
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↗
PubMed1983

Renal cell carcinoma: the Ochsner Medical Institution experience (1945-1978).

We reviewed 161 patients operated upon for renal cell carcinoma between 1945 and 1978. Life table and survival analyses were computed to compare the effects of stage, tumor differentiation, cell type, surgical technique, renal vein involvement and sex on the years of survival. Patients with stage I and well differentiated tumors had the best prognosis. All patients surviving 10 years or more had well differentiated tumors. The type of nephrectomy did not affect survival and lymphadenectomy was only of value in staging the disease. The stage and differentiation of the tumor were more important to outcome than choice of therapy.

Adenocarcinoma↗