The small for dates infant.
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Birth Weight↗
Biomedical subjects
M Gallagher
Publications and source records attributed to M Gallagher.
Congenital toxoplasmosis--a case report.
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Female↗
Relationship of age-related decline across several behavioral domains.
These studies were designed to assess whether aged rats have a similar degree of impairment across a number of behavioral tasks. In Experiment 1, no relationship between the severity of a spatial learning impairment and reaction time performance was found among aged rats. This result is in contrast with a relationship that was found in aged rats between spatial learning and the rate of recovery from gustatory neophobia (results of Experiments 2 and 3). Experiment 3 further showed that the relative spatial learning abilities of two subgroups of aged rats, i.e., "impaired" and "unimpaired," were related to transfer training in the water maze conducted six weeks after the completion of original training. The subgroups of aged animals were also distinguished by their latencies (but not errors) on a circular holeboard maze, and the pattern of water consumption during the light/dark cycle determined at the end of the entire protocol (13th week of testing). Other measures, however, did not distinguish the aged subgroups that were formed on the basis of spatial learning ability.
Aging↗
Markers for biogenic amines in the aged rat brain: relationship to decline in spatial learning ability.
The major goal of the study was to evaluate the relationship of brain aging to individual differences in functional decline in rats. Forebrain choline-acetyltransferase (ChAT) and monoamines, including their metabolites, were examined in young and aged male Long-Evans rats in relation to their spatial learning ability. Aged rats that were unimpaired on a spatial learning task exhibited few changes in neurochemistry relative to the young group: each change in this subgroup was also evident in the remaining aged animals that were behaviorally impaired. Additional changes in neurochemical measures only found in the behaviorally impaired aged animals included decreased ChAT in the basal forebrain, striatum, and frontal cortex. A cluster analysis using the 15 neurochemical measures that were sensitive to aging yielded groupings of aged animals that differed with respect to their spatial learning ability, but not in their cue learning latencies. In this analysis the activity of ChAT in the basal forebrain and striatum appeared to be the best predictors of spatial learning impairment.
Aging↗
A longitudinal study of reaction time performance in Long-Evans rats.
This study was undertaken to examine individual differences in the progression of age-related decline on a measure of sensorimotor function. Twenty-one adult rats were trained on a simple reaction time (RT) task and assessed every 6 weeks from 14.5 to 25 months of age. An overall slowing of RT latencies associated with chronological age was observed. However, some rats maintained a stable performance with age while others slowed considerably. Another measure within the RT task, accuracy of performance, appeared to represent a stable individual characteristic that was insensitive to the effects of age. However, no measure of performance on the RT task at 14.5 months of age predicted later impairment in RT latency. At the completion of longitudinal testing, spatial learning in the Morris water maze was assessed in these aged rats along with a young comparison group. The aged rats were impaired relative to young controls in locating the escape platform. Measures of cognitive function and sensorimotor function within the spatial task were, however, unrelated to slowing of RT latency.
Aging↗
Issues in the development of models for cognitive aging across primate and nonprimate species.
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Aging↗
Cholinergic binding sites in rat brain: analysis by age and cognitive status.
Age-related alterations in the density of cholinergic receptor binding and reuptake sites were examined in discrete forebrain regions of behaviorally tested rats using quantitative autoradiography. Neurochemical changes associated with chronological age alone were distinguished from memory-dependent alterations by correlating density of binding sites with performance in the Morris water maze task. An initial analysis of tritium quenching indicated no reliable differential quenching in the study population. Modest age-related reductions in selected subtypes of cholinergic binding sites in basal forebrain, basal ganglia, and thalamus were observed. However, these reductions were not correlated with a spatial memory deficit. In contrast, no significant changes in the analysis by chronological age were detected for the density of [3H]hemicholinium binding to high affinity choline uptake sites or [3H]pirenzepine binding to M1 receptors in any brain region but strong correlations were found between behavioral performance of aged rats and density of these sites in dorsal hippocampal subfield CA3 and dentate gyrus. These findings indicate the value of combined neurobiological/behavioral assessment.
Aging↗
Mesostriatal dopamine markers in aged Long-Evans rats with sensorimotor impairment.
Changes in the mesostriatal dopamine system associated with normal aging are observed in both human and laboratory animals, but the specific behavioral consequences of these nonpathological changes are largely unexplored. The present study (a) assessed the effects of normal aging on markers for the mesostriatal dopamine system, and (b) examined the relationship of age-related changes in this system to decline in reaction time performance. Decreased levels of midbrain dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) were observed in the aged rats as compared to young, but there was no evidence for age-related changes in the density of D1 or D2 receptor binding or the density of dopamine uptake sites. Some differences were observed when the aged rats were grouped according to reaction time performance. Aged RT-unimpaired rats exhibited higher density of D1 binding in rostrodorsal striatal patch areas, but lower overall levels of DA. In caudal striatum, aged RT-unimpaired rats exhibited lower DA and higher DOPAC levels.
3,4-Dihydroxyphenylacetic Acid↗
Hippocampal muscarinic receptor function in spatial learning-impaired aged rats.
Efficiency of coupling of hippocampal muscarinic receptors to phosphoinositide (PI) turnover was investigated in behaviorally characterized young and aged Long-Evans rats using hippocampal minces and the method of partial receptor alkylation of Furchgott. Densities of the m1, m2, and m3 receptor proteins were determined using specific antibodies and immunoprecipitation. Spatial learning ability was quantified using a water maze. There were no differences in the levels of muscarinic receptor proteins between young and aged (27 months) rats or in rats with impaired spatial learning. The dissociation constant (KD) for the agonist oxotremorine-M and the KD/EC50 ratio, an indicator of receptor-effector coupling efficiency were similar in young and aged rats. However, the maximal PI turnover response to oxotremorine-M was decreased in impaired aged rats and this parameter was highly correlated with the spatial learning index (R = -0.825; p < 0.001). A reduction in effector stimulation in the absence of changes in receptor protein or coupling efficiency suggests that dysfunction in the hippocampal muscarinic receptor systems occurs at the level of phospholipase C or beyond.
Aging↗
Neurobiological substrates of behavioral decline: models and data analytic strategies for individual differences in aging.
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Age Factors↗
A re-examination of the role of basal forebrain cholinergic neurons in spatial working memory.
The basal forebrain cholinergic system, which innervates widespread cortical and limbic structures, has traditionally been considered important for learning and memory. The use of an immunotoxin, 192 IgG-saporin, has brought this functional designation into question; selective immunolesions of basal forebrain cholinergic neurons have failed to reproduce a number of behavioral deficits that were observed with less selective lesion methods. Recent reports, however, have indicated that a mild impairment is observed in rats on a spatial working memory task after 192 IgG-saporin lesions of the rostral groups of cholinergic neurons located in the medial septal area (MSA). Those studies used a lesion protocol in which a single large volume injection of the immunotoxin was made into the MSA. In the current study, multiple small injections were made at the locations of cholinergic neurons in the MSA, producing a cholinergic depletion comparable to that reported in the earlier studies where deficits were observed. In the current study, however, rats with cholinergic lesions had no impairment in the spatial working memory task, even when delays ranging from 60 s to 8 h were imposed within a trial. The current report indicates that selective removal of cholinergic neurons in the basal forebrain may not be sufficient to produce a deficit in spatial working memory.
Animals↗
Effect of age and cognitive status on basal level AP-1 activity in rat hippocampus.
Activator protein-1 (AP-1) was examined at multiple levels (mRNA, DNA binding, composition) in hippocampus of young and aged rats that were behaviorally characterized for spatial memory. GFAP mRNA was measured as a gene product known to increase with aging and to be regulated by AP-1. The activity of Jun-amino terminal-kinase (JNK) was also assessed. Levels of c-jun and c-fos mRNAs were unchanged with aging or spatial learning ability. Abundance of GFAP mRNA was significantly increased in aged hippocampus but did not correlate with spatial learning. Total AP-1 binding activity was unaltered with age or cognitive ability. In hippocampus of young, aged unimpaired and aged impaired rats, AP-1 consists mainly of c-Jun, phosphorylated c-Jun (p-c-Jun), JunD, and smaller amounts of c-Fos. JNK is constitutively active in young and aged hippocampus. We conclude that the basal expression of c-fos and c-jun mRNA, overall AP-1 binding activity and AP-1 composition are not influenced by aging or cognitive ability.
Aging↗
Place cell rigidity correlates with impaired spatial learning in aged rats.
In humans and in animals, some aged individuals are severely impaired in learning and memory capacity whereas others perform as well as young adults. In the present study, the spatial memory capacity of young and aged rats was characterized by the Morris water maze task, and then firing patterns of hippocampal "place cells" were assessed as the animals explored a familiar environment and a geometrically-altered version of the environment. Spatial representations of hippocampal cells in young and memory-intact aged rats changed upon exposure to the altered environment. In contrast, spatial representations of many cells in aged, memory-impaired rats were unaffected by the environmental alteration. Furthermore, combining all groups, the extent to which spatial representations distinguished the familiar and altered environments predicted learning capacity in the water maze. These findings suggest that a major component of memory impairment in aging may be the failure of the hippocampus to encode subtle differences in contextual information that differ across multiple experiences, such as the sequence of training trials in the water maze.
Aging↗
An age-related spatial learning deficit: choline uptake distinguishes "impaired" and "unimpaired" rats.
A functional decline in the hippocampal formation may underlie the emergence of spatial learning deficits in aged rodents. In this study, sodium-dependent high-affinity choline uptake (HACU) was used to monitor hippocampal function in response to training on a spatial task. The subjects were male Long-Evans rats at either 4 months or 22-24 months of age. Animals were trained to locate a camouflaged escape platform in the Morris water maze. Each animal that received place training had a yoked counterpart that was exposed to swimming in the maze but was not required to learn the task. Animals, both young and aged, were sacrificed after attaining a criterion performance. Relative to animals in the yoked condition, place training significantly reduced HACU in both the young rats and in a subpopulation of the aged animals that learned the task rapidly. In contrast, for aged rats that had an impaired rate of acquisition, no effect of place training on HACU was observed. These results provide evidence for a relationship between the behavioral capacities of aged rats and changes in the status of hippocampal function.
Aging↗
Spatial learning deficits in old rats: a model for memory decline in the aged.
Spatial learning tasks are sensitive to functional decline in aged laboratory rodents. This is a review of recent work that has examined both the nature of age-related impairments on spatial tasks, and the relation of such deficits to underlying neurobiological mechanisms. The review supports the notion that hippocampal dysfunction underlies the mild/moderate cognitive decline that often accompanies normal aging. Thus the spatial learning deficit in aged rodents is a promising model for understanding the effect of age on brain systems that serve a memory function in humans.
Aging↗
Evaluation of muscarinic M2 receptor sites in basal forebrain and brainstem cholinergic systems of behaviorally characterized young and aged Long-Evans rats.
Aged (23-25-month-old) male Long-Evans rats were assessed for deficits in spatial cognition relative to young (4-6-month-old) rats. An in vitro autoradiography study was then conducted for muscarinic M2 sites using [3H]AF-DX 384 to assess binding in basal forebrain and brainstem areas where cholinergic neurons are localized. The analysis of basal forebrain included the medial septal/diagonal band region that provides cholinergic innervation of the hippocampus; the laterodorsal tegmental nucleus and pedunculopontine tegmental nucleus were analyzed in the brainstem. A significant age-related reduction in M2 binding was found in both the basal forebrain and brainstem. Only the reduction in the basal forebrain, however, was correlated with spatial learning impairment. Although the basal forebrain and brainstem cholinergic systems are each vulnerable in normal aging, contributions to the behavioral effects of aging may be distinctive for the two systems.
Aging↗