Cytogenetic variability in radiation induced mouse leukaemia.
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Animals↗
Biomedical subjects
C A Barnes
Publications and source records attributed to C A Barnes.
Cytogenetic techniques in radiobiological procedures.
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Animals↗
Selective improvement of aged rat short-term spatial memory by 3,4-diaminopyridine.
Young (10 month) and old (28 month) Fischer 344 rats were injected (IP) with 3,4-diaminopyridine (3,4-DAP) or saline 10 minutes before training on two tests of spatial memory (the Barnes circular platform and the radial 8-arm maze). This agent has been found to block potassium channels in neurons, thereby increasing calcium influx, prolonging the action potential, and leading to increased transmitter release. The circular platform task assessed the drug's effect on spatial reference memory over 24 hour intertrial intervals, and the radial maze assessed its effect on short-term working memory within a 5 minute test session. 3,4-DAP was found to selectively improve memory performance of the old animals, and, within that age group, only improved performance on the short-term memory task. 3,4-DAP may therefore be effective for only a restricted set of age-related memory problems.
4-Aminopyridine↗
Acetyl-1-carnitine. 1: Effects on mortality, pathology and sensory-motor performance in aging rats.
Three different test sites assessed the effects of acetyl-1-carnitine (AC) on age-related changes in general health, sensory-motor skills, learning, and memory. Two groups of rats began the experiments at 16 months of age. One group (OLD-AC) was given AC, 75 mg/kg/day, beginning at 16 months. The other group (OLD-CON) was treated identically except it was not given the drug. Beginning at 22 months of age, these rats and a group of young (3-4 months old) rats (YG-CON) were given a series of sensory-motor tasks. AC decreased mortality, and had no reliable effect on body weight, fluid intake, or the general health of the rats. These data indicate that a chronic dose of AC does not interfere with food and water intake, and may increase longevity. An age-related decline of performance occurred in most of the sensory-motor tasks; locomotor activity was reduced in a novel environment and in a runwheel, and the ability to prevent falling was reduced in tests on a taut wire, rotorod, inclined screen, and several types of elevated bridges. An age-related decline of performance did not occur in grooming, or in the latency to initiate several different behaviors. AC had no effect on performance in any sensory-motor task. These data indicate that the improvements produced by AC in some tests of spatial memory may be due to the effects of AC on cognitive abilities rather than on sensory-motor skills.
Acetylcarnitine↗
Acetyl-1-carnitine. 2: Effects on learning and memory performance of aged rats in simple and complex mazes.
Acetyl-1-carnitine (AC) was administered via drinking water for six months to one group (OLD-AC) of male F-344 rats beginning at 16 months of age, while another group (OLD-CON) of rats was given water only during that period. The rats were maintained on this treatment throughout behavioral testing, which began at 22 months of age. Performance of the OLD-AC and OLD-CON rats was compared to that of young control (YG-CON) rats on the following set of tasks: spontaneous alternation in the arms of a T-maze, two-choice simultaneous discrimination in the stem of a T-maze, rewarded alternation in the arms of a T-maze, spatial discrimination and reversal on a circular platform, spatial working memory in the radial 8-arm maze, long-term memory in the 14-unit T-maze, and for preference of the light or dark chamber of a two-compartment box. AC improved the long-term memory performance in the split-stem T-maze and on the circular platform but had no discernable effects on performance of aged rats in the other tasks. Possible reasons for the selectivity of this agent's action on behavior are suggested.
Acetylcarnitine↗
Exercise does not modify spatial memory, brain autoimmunity, or antibody response in aged F-344 rats.
Old F-344 rats were given endurance training over a 10-week period on a motorized treadmill. This treatment resulted in substantial heart-to-body weight ratio increases, indicative of effective training. To determine whether endurance training might alter some of the known immune system and cognitive changes observed during aging, exercised old rats were compared to nonexercised old and young controls on three variables: in vivo antigen-specific immune activity, brain-reactive antibody formation, and spatial memory. The exercise training did not influence any of these measures in the old rats. Both groups of old rats showed poorer antibody response to a specific antigen, more brain-reactive antibody formation, and poorer spatial memory than the young controls. There was, however, a significant relationship between brain-reactive antibody formation and spatial memory performance, regardless of training condition.
Aging↗
Increase in perforant path quantal size in aged F-344 rats.
The data presented here confirm and extend the evidence for fewer, but stronger, perforant path synaptic connections onto the granule cells of the hippocampus in old F-344 rats. The old animals used in the present report were drawn from a population that showed deficits in the retention of a spatial problem in the Morris water task. Using the method of minimal-stimulation of perforant path afferents, unitary granule cell EPSPs were found to be larger in the 25-month than in the 6- and 9-month age groups. Furthermore, applying statistical methods for quantal analysis, data are presented that suggest that the larger synaptic responses of the old rats come about through an increase in quantal size. These experiments therefore suggest that individual synapses become more powerful in the perforant pathway of old rats, and that this strengthening occurs through an increase in quantal size. The implications of these findings for hippocampal information processing are discussed.
Aging↗
Differential effects of age on subpopulations of hippocampal theta cells.
The possible contribution of age-related changes in the firing properties of hippocampal theta cells to spatial learning deficits was addressed in the present study. The behavioral correlates of theta cells in strata oriens, pyramidale, and granulosum were compared as young and old rats performed a radial maze spatial working memory task. Behaviorally, the old animals made significantly more errors on the maze and required more time to solve the task than did young animals. Firing rates were compared in four different locomotion states: still, running radially inward and radially outward, and forward motion. The discharge rates of theta cells in strata pyramidale and granulosum were significantly modulated by these movements in both age groups. Stratum oriens theta cells recorded from young animals, on the other hand, were not movement-sensitive, while similar cells from old animals demonstrated exaggerated responses to movement. In old animals, the mean discharge rates were higher in stratum granulosum and lower in stratum oriens than in the young rats. The discharge rates of cells in stratum pyramidale did not differ between age groups. These region specific changes in the firing characteristics of hippocampal theta cells are likely to have important consequences for information processing in this structure.
Aging↗
Effects of age on L-glutamate-induced depolarization in three hippocampal subfields.
The effects of aging on the translation of L-glutamate-induced depolarization into hippocampal neuronal firing frequency were studied in vitro. L-glutamate was iontophoretically-applied to the somatic region of extracellularly recorded single units. In none of the three principal hippocampal subfields (fascia dentata, CA3, and CA1) were there any effects of age on neuronal sensitivity to L-glutamate. Because there are pronounced, region-specific age effects on AMPA sensitivity (3), these results are in agreement with the conclusions of other investigators that the depolarization caused by exogenously applied L-glutamate probably exerts its effects through nonsynaptic mechanisms. These mechanisms, however, which lead to powerful depolarization and action potentials in hippocampal cells, are unaffected by age.
Action Potentials↗
Acetyl-L-carnitine: behavioral, electrophysiological, and neurochemical effects.
Aged rats were chronically administered acetyl-L-carnitine (AC) for 10 months. During this period they were tested on learning and sensorimotor tasks and were then subsequently tested electrophysiologically to assess induction and decay rates of long-term synaptic enhancement (LTE) in the hippocampus. Four groups were tested: young controls (4 mo-con), middle-aged controls (16 mo-con), old controls (24 mo-con), and old AC-treated rats (24 mo-AC). After completion of electrophysiological testing, each rat was sacrificed and investigated for age- or drug-related changes in three neurotransmitter markers; including, NMDA-sensitive glutamate receptors, high affinity choline uptake, and adenosine receptor number in the neocortex, hippocampus or caudate nucleus. Aging impaired spatial learning and there was a robust positive correlation between NMDA receptors in the hippocampus and acquisition of the spatial learning task. Induction of hippocampal LTE was reduced in 24 mo-AC rats and NMDA receptor number and high-affinity choline uptake in the frontal cortex was increased. Several suggestions are offered to explain the action of AC on these neurobiological parameters in old rats.
Acetylcarnitine↗
Age-related decrease in cholinergic synaptic transmission in three hippocampal subfields.
The present study was designed to examine the effect of age on cholinergic synaptic transmission in the three principal hippocampal subregions, and to assess whether these effects covary with age-related behavioral deficits. Young (3 week), adult (9 month), and old (24-27 month) rats were first tested on the Morris water task, and most of the old rats were severely impaired on the spatial version. The cholinergic slow epsp was induced by tetanic stimulation of stratum oriens or stratum granulosum, and recorded intracellularly in vitro from CA1 and CA3 pyramidal cells and granule cells in the fascia dentata (FD). The amplitude of the slow epsp was significantly reduced in old rats in all areas (CA1 59%; CA3 55%; and FD 56%). This age-related decrease was also present following the blockade of glutamatergic and GABAergic transmission, ruling out possible artifactual contributions from these systems to the change in the slow epsp. Our data suggest that functional cholinergic transmission is compromised in all areas of the hippocampus during normal aging. Few statistically significant correlations, however, were found between the age-related deficit in spatial learning and the decrease in cholinergic synaptic function.
Aging↗
LTP induction threshold change in old rats at the perforant path--granule cell synapse.
Old, memory-deficient rats do not show a change in the threshold for long-term potentiation (LTP) induction in hippocampal region CA1. This observation suggests that defective NMDA receptor mechanisms at the Schaffer collateral-CA 1 pyramidal cell synapse cannot explain age-related LTP induction deficits that are observed under some stimulation protocols. The effects of aging on functional electrophysiology are not, however, identical between hippocampal subregions. In fact, at the perforant path-granule cell synapse of rats NMDA receptor-mediated responses are reduced, suggesting a possible change in the threshold for LTP induction at this synapse. This hypothesis was tested in the present experiment. We found that when weak orthodromic stimulation of medial perforant path fibers is paired with intracellular current injection of granule cells, the threshold for LTP induction is elevated in aged, spatial memory-impaired rats compared to middle-aged and young controls. Thus, in addition to there being fewer total medial perforant path synaptic contacts in old rats, greater depolarization and input convergence is required before durable modification of synaptic strength can be induced.
Action Potentials↗
Selective decline in protein F1 phosphorylation in hippocampus of senescent rats.
Certain forms of neuronal plasticity have been found to be expressed through alterations in brain protein phosphorylation, and its regulation by protein kinase activity. Of interest in this regard is the possibility that the decline in neuronal plasticity and cognitive function that occurs in advanced age may result in part from altered phosphorylation of specific proteins. As a first attempt to identify age-related changes in phosphoproteins, we assayed in vitro phosphorylation of proteins in hippocampus, cerebellum, entorhinal cortex, and frontal cortex from Fischer-344 rats of 5 months, 11 months, and 25 months of age. Compared to the middle-aged animals, the aged rats showed a selective 46% decline in phosphorylation of the 47 kDa protein (F1) in hippocampus, with no change in the phosphorylation of other proteins measured in this structure. Aged animals also showed decreased phosphorylation relative to young animals. No age-related change was observed in any protein band for the other brain areas examined. Since protein F1 is phosphorylated by protein kinase C (PKC), the cytosolic and membrane distribution of this enzyme was compared across age groups. The activity of PKC in hippocampus did not change across age. The explanation of this age-related decline in protein F1 phosphorylation is likely to be a decline in the substrate protein itself. The results are discussed in terms of protein F1's possible role in age-related decline of hippocampal synaptic plasticity.
Aging↗
Aging and the physiology of spatial memory.
Evidence for age-related changes in spatial memory in rodents and humans is presented, along with data that suggest that the hippocampal formation is necessary for normal performance on spatial tasks in both species. An examination of the electrophysiological characteristics of this structure in rats suggests that the changes that occur with age in the hippocampus are selective, but that at least two primary types of alterations contribute to the spatial cognitive impairment seen in these animals. These include a deficit in the ability to maintain synaptic enhancement and a reduction in the accuracy of information processing ability of single hippocampal neurons.
Aging↗
Age-related decrease in the N-methyl-D-aspartateR-mediated excitatory postsynaptic potential in hippocampal region CA1.
Glutamatergic fast synaptic transmission is known to be altered with age in a region-specific manner in hippocampus of memory-impaired old rats. In the present experiment, presynaptic fiber potentials and non-N-methyl-D-aspartate (NMDAR) and NMDAR-mediated synaptic responses in CA1 were compared in three ages of behaviorally characterized male F-344 rats. In the CA1 region, old rats showed approximately equivalent reductions in non-NMDAR- and NMDAR-excitatory postsynaptic potential amplitudes for a given size of presynaptic fiber potential. There was no change in magnitude of the presynaptic response itself at any stimulus level. These results are consistent with the hypothesis that there is a reduction in the number of Schaffer collateral synapses per presynaptic axon. This pattern of results in CA1 is very different from what is known to occur at the perforant path-granule cell synapse. In fascia dentata the non-NMDAR-mediated excitatory postsynaptic potential is increased in amplitude, although the NMDAR-mediated excitatory postsynaptic potential is reduced for a given presynaptic input. These data suggest that age-related functional alterations in neurotransmitter receptor subtypes occur differentially between closely-related anatomical subregions.
Aging↗
Do synaptic markers provide a window on synaptic effectiveness in the aged hippocampus?
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Aging↗
The neurobiology of memory changes in normal aging.
Cognitive alterations occur over the lifespan of every species studied and have been quantified carefully in humans, other primates and rodents. Correspondingly, changes in hippocampal function have been associated with a number of observed memory impairments across species. It appears that humans, alone, show Alzheimer's disease-like cognitive and neural pathology spontaneously. Thus, a comparison of normal age-related changes in cognition in other animals can help disambiguate the boundary between normal and pathological states of aging in humans. Another important contribution made from studying aging in non-human species is the ability to examine, in more detail, the basic neural mechanisms that may be responsible for brain aging in these species. So far, most of the functional neurobiological studies have been conducted in the aged rat. We propose that the link between rodent and human work can be made much stronger by combining neurophysiological and behavioral investigation of normal aging in the non-human primate.
Aged↗
Effects of aerosol-vapor JP-8 jet fuel on the functional observational battery, and learning and memory in the rat.
To determine whether JP-8 jet fuel affects parameters of the Functional Observational Battery (FOB), visual discrimination, or spatial learning and memory, the authors exposed groups of male Fischer Brown Norway hybrid rats for 28 d to aerosol/vapor-delivered JP-8, or to JP-8 followed by 15 min of aerosolized substance P analogue, or to sham-confined fresh room air. Behavioral testing was accomplished with the U.S. Environmental Protection Agency's Functional Observational Battery. The authors used the Morris swim task to test visual and spatial learning and memory testing. The spatial test included examination of memory for the original target location following 15 d of JP-8 exposure, as well as a 3-d new target location learning paradigm implemented the day that followed the final day of exposure. Only JP-8 exposed animals had significant weight loss by the 2nd week of exposure compared with JP-8 with substance P and control rats; this finding compares with those of prior studies of JP-8 jet fuel. Rats exposed to JP-8 with or without substance P exhibited significantly greater rearing and less grooming behavior over time than did controls during Functional Observational Battery open-field testing. Exposed rats also swam significantly faster than controls during the new target location training and testing, thus supporting the increased activity noted during Functional Observational Battery testing. There were no significant differences between the exposed and control groups' performances during acquisition, retention, or learning of the new platform location in either the visual discrimination or spatial version of the Morris swim task. The data suggest that although visual discrimination and spatial learning and memory were not disrupted by JP-8 exposure, arousal indices and activity measures were distinctly different in these animals.
Administration, Inhalation↗