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L A Hyde

Publications and source records attributed to L A Hyde.

At least 19 recordsLinked to original sources

Ts65Dn mice, a model for Down syndrome, have deficits in context discrimination learning suggesting impaired hippocampal function.

The Ts65Dn mouse is segmentally trisomic for a part of mouse chromosome 16 and is a genetic model for Down syndrome and Alzheimer's disease. Although many studies have examined the learning and memory processes in Ts65Dn mice, it has yet to be determined if Ts65Dn mice are specifically impaired in learning tasks that require an intact hippocampus. Context discrimination learning is dependent on the dorsal hippocampus in mice. In this task, mice learn to discriminate two similar contexts, one of which is associated with foot shock. In the current study, Ts65Dn mice learned almost identically to what has been reported for mice with dorsal hippocampal lesions, while controls behaved similarly to sham lesioned mice. Therefore, Ts65Dn mice have learning deficits in a hippocampal dependent task that may be related to the loss of cholinergic input to the hippocampus, which occurs after 6 months of age.

Age Factors↗

Motor learning in Ts65Dn mice, a model for Down syndrome.

Ts65Dn mice are a genetic model for Down syndrome. Both individuals with Down syndrome and Ts65Dn mice have reduced cerebellar volumes and the cerebellum is involved in motor learning. Conflicting results have been reported on the motor learning abilities of Ts65Dn mice, which may be related to procedural differences between the motor learning tasks used in different laboratories and/or variability in phenotype because of the segregating background on which the mice are maintained. In this study, we examined learning in three types of motor tasks (peg running, accelerating rotorod, and rotating rod) which were initially easy for mice and gradually increased in difficulty. Ts65Dn mice learned the peg running task as well as controls, and learned the accelerating rotorod and rotating rod tasks as well as, and even better than, controls. These data indicate that Ts65Dn mice are not impaired in motor learning.

Animals↗

Avoidance learning in autoimmune mice.

Previous studies have shown that autoimmune mice perform very poorly on active avoidance learning tasks. In the current studies, mice with lupus-like systemic autoimmunity were able to learn active, as well as passive, avoidance protocols with shock as reinforcement. Therefore, the behavioral deficits seen in active avoidance tasks are not a consequence of the use of electric shock. Rather, the current findings suggest that the inability of autoimmune mice to learn shock motivated responding is due to multiple performance factors, including shock level and properties of the testing apparatus.

Animals↗

Non-spatial water radial-arm maze learning in mice.

Recently, we published a method for examining working and reference memory in mice using a spatial version of the water radial-arm maze. Here we describe a non-spatial version of the same maze. BXSB mice were able to learn the maze as shown by the decrease in the number of working and reference memory errors over sessions. This maze was used to examine learning differences between males and females and between mice with misplaced clusters of neurons in layer I of cortex (ectopias) and those without. In a prior study using the spatial version of the water radial-arm maze, male BXSB mice had poorer working memory than females during the acquisition phase. Similarly, in this study male BXSB mice demonstrated impaired working memory during the asymptotic phase of non-spatial radial-arm maze learning. Two prior studies showed that mice with neocortical ectopias demonstrated working memory impairments compared to non-ectopic littermates in the spatial version of the water radial-arm maze. Contrary to this, in the non-spatial radial-arm maze used here, ectopic mice were not impaired in working memory and showed better memory when the working memory 'load' was the highest. Overall, both versions of the maze can be useful tools to assess spatial and non-spatial working and reference memory in mice.

Animals↗

Spatial ability of XY sex-reversed female mice.

Perinatal gonadal hormones significantly affect subsequent sex differences in reproductive and non-reproductive behaviors in rodents. However, the influence of the sex chromosomes on these behaviors has been largely ignored. To assess the influence of the non-pseudoautosomal region of the Y chromosome, C57BL/JEi male and female mice and mice from the C57BL/6JEi-Y(POS) consomic strain were given behavioral tests known to distinguish males from females. The C57BL/6JEi-Y(POS) strain contains sex-reversed XY-females which, when compared to their XX-female siblings, allow assessment of the influence of the Y chromosome in a female phenotype. XX-females and XY-females did not differ on open-field activity, the Lashley maze, or active avoidance learning, but XY-females were significantly better than XX-females on the Morris hidden platform spatial maze. These findings suggest that males may have both a genetic and a hormonal mechanism to ensure visuospatial superiority.

Animals↗

Effects of the non-pseudoautosomal region of the Y-chromosome on behavior in female offspring of two congenic strains of mice.

The learning behavior of female offspring of two strains of mice congenic for the Y-chromosome, BXSX/MpJ-Yaa and BXSB/MpJ-Yaa+, was examined. Significant differences were found in the Morris water maze and the Lashley III maze, demonstrating that the fathers' Y-chromosome can indirectly affect their daughters' behavior. Approximately half the mice had neocortical ectopias, and females from the two paternal groups reacted differently to the presence or absence of ectopias. Since females do not have a Y-chromosome, these effects must be through non-genetic mechanisms. Prenatal factors that could have played a role include possible differences in gonadal growth and the presence of different H-Y antigens. Postnatally, the sires and male siblings of the two strains may not have behaved the same toward the female offspring and/or the dams, creating differences in behavior. In summary, the behavior of female offspring of two groups of males, genetically the same except for their Y-chromosomes, was examined. Since females do not receive a Y-chromosome from their fathers, in theory their behavior should not differ. Significant differences were found, indicating that the Y-chromosome, through some indirect mechanism, can affect females of the next generation.

Animals↗

BXSB mice can learn complex visual pattern discriminations.

To determine if mice could perceive differences among several complex black/white patterns, a water version of a radial-arm maze was modified into a T-maze. BXSB mice were able to discriminate between multiple pairs of stimuli.

Analysis of Variance↗

Effects of neocortical ectopias upon the acquisition and retention of a non-spatial reference memory task in BXSB mice.

BXSB mice have a 40-60% incidence of small, focal, neocortical dysplasias called ectopias. Ectopics and non-ectopics were compared on horizontal-vertical discrimination learning, a non-spatial cognitive task. No differences were found during acquisition. Ectopic mice, however, were superior when retested 8 weeks later. The results support prior findings that ectopic mice have better long-term spatial memory and extend this conclusion to the non-spatial domain.

Animals↗

Water version of the radial-arm maze: learning in three inbred strains of mice.

The conventional land radial-arm maze has several disadvantages, including requiring a complicated automated apparatus, the elimination of odors as cues, and the use of food deprivation. We have created a water version of the maze, based on the principles of the land version, which maintains the advantages and excludes some of the disadvantages. In our maze, BXSB and C57BL/6 mice significantly reduced the number of working and reference memory errors committed over sessions, while NZB mice did not. For each strain, as the working memory 'load' increased during a session, the number of errors increased. However, with practice the BXSB and C57BL/6 strains were able to handle this memory load more effectively. Mice were able to learn the maze without extensive adaptation, training, or testing and they did not exhibit 'chaining'. This maze can also be considered to be an example of a water win-shift task that mice can easily learn. Therefore, the water version of the radial-arm maze can be a simple and useful tool for studying rodent learning and memory.

Animals↗

Learning in year-old female autoimmune BXSB mice.

BXSB/ MpJ-Yaa and NZB/BINJ mice have been used as animal models for both developmental learning disability and systemic autoimmune disease. Approximately 40-60% of these animals show ectopic clusters of neurons in Layer I of cortex similar to those found in postmortem analyses of human dyslexics, and all exhibit an autoimmune condition similar to systemic lupus erythematosus (SLE) in humans. The expression of immune disease in the BXSB strain, unlike in humans, is more severe in males than females. Most previous studies have examined the behavioral sequelae of neocortical ectopias at a relatively young age, when the BXSB females (unlike the male BXSB and female and male NZBs) are not yet showing high titers of autoantibodies associated with their lupus-like form of autoimmune disease. This study examined the behavior of BXSB females at an age subsequent to autoimmune disease onset. When contrasted with younger animals, year-old BXSB females showed good learning behavior, with no differences in Lashley maze learning and remarkably good performance in a visual discrimination learning task. These results are consistent with other data which indicate that many types of learning behavior are apparently unperturbed by systemic autoimmune disease. Results also showed significant interactions between a measure of lateral paw preference and the presence or absence of ectopias in Lashley maze learning. Animals without ectopias that exhibited a right lateral paw preference showed the greatest number of errors on a number of test measures. These findings support previous results indicating that behavioral effects associated with ectopias may vary based upon the behavioral laterality of affected animals.

Age Factors↗

Lack of shuttlebox avoidance learning in autoimmune BXSB mice: a test of learned helplessness.

1. The authors investigated whether learned helplessness was a possible explanation for the observed learning deficits demonstrated by autoimmune mice in shuttlebox avoidance. If mice were experiencing learned helplessness during the avoidance testing, one would expect this to transfer to other behavioral tests resulting in lower learning scores. 2. One group of BXSB mice was tested in avoidance first, a water version of the Lashley III maze second, and water escape last, while another group was given these tests in the reverse order. 3. Animals who were exposed to avoidance first did not demonstrate any learning deficits in subsequent tests, suggesting that there were no adverse effects of avoidance training on later water maze learning. 4. However, correlations between number of null responses during avoidance learning and two other measures suggest that the null response measure may be an index of a continuum of learned helplessness within the BXSB strain.

Animals↗

Absence of postnatal testosterone fails to demasculinize the male rat's corpus callosum.

We had previously shown that elimination of testosterone from embryonic day 17 through adulthood reduced the midsagittal area of the male rat corpus callosum (CC). However, day 1 castration, performed after the 2-h post-birth testosterone surge, was without effect. To elucidate the contribution of this surge on the CC, male rats were delivered by cesarean section and castrated within 20 min. This procedure eliminated the 2-h postnatal rise in testosterone levels. The prenatal surge in testosterone, which occurs on embryonic day 18, remained intact. In adulthood, callosal area was examined in castrate males, sham males, and intact females. Castrate males and sham males had significantly larger CCs as compared to females. The two male groups did not differ from each other. Body weight was significantly higher in sham versus castrate males, establishing the effectiveness of the castration. These results show that hormonal organization of the CC in the male is the result of the independent action of prenatal testicular androgens, and suggest that the end of this period marks the end of callosal sensitivity to testicular hormone influence. In addition, this report documents sexual dimorphism of the CC in a third rat strain.

Analysis of Variance↗

Learning and memory in the autoimmune BXSB mouse: effects of neocortical ectopias and environmental enrichment.

Approximately 40-60% of BXSB mice have ectopic cell clusters in layer 1 of neocortex. Prior studies have shown distinct behavioral differences between those with ectopias and their non-ectopic littermates. In this study, female BXSB mice were reared after weaning in either enriched environments or standard cages. Following an initial round of behavioral testing, all mice were housed in standard cages and retested. Enriched cage mice (both ectopic and non-ectopic) showed increased activity, greater speed, and enhanced learning scores across a variety of tests. Additionally, prior test experience itself had significant positive effects on Hebb-Williams maze learning. The presence of ectopias resulted in better Morris maze learning for standard cage reared mice. Further, ectopic mice, regardless of their housing condition, showed better long-term retention in the Morris maze than did their non-ectopic counterparts. These findings show that abnormalities in corticogenesis need not always result in functional deficit.

Analysis of Variance↗

A computer-aided procedure for measuring Hebb-Williams maze performance.

We describe a shortened procedure for testing mice over a 5-day interval on a swimming version of the Hebb-Williams maze. The mice are given 1 day of adaptation training, and are tested over the next 4 days on Hebb-Williams problems 1, 6, 12, and 5, in that order. As an animal swims through one of the maze problems, the computer screen shows the maze pattern, and an observer traces the path taken with a computer mouse. The computer program, Observe Software, stores the path sequence, determines the error score for that trial, and sends the information to a spreadsheet where it is available for statistical analyses.

Animals↗

Lack of activational influence of ovarian hormones on the size of the female rat's corpus callosum.

The sex difference in the midsagittal area of the adult rat corpus callosum (CC) has been shown to be mediated, in part, by gonadal steroids in early development, with the sensitive period of hormone action in the female extending at least up to postnatal day 25. Given this prolonged sensitivity, the current study attempted to delineate organizational vs. activational influences of gonadal hormones on the female rat CC. In Experiment 1, callosal size was examined across the estrous cycle at 52 and 90 days of age. In Experiment 2, females were ovariectomized at 78 days and CC parameters assessed at 110 days. Last, in Experiment 3, females were ovariectomized at 78 days and sacrificed at 110 days; in addition, sham females were sacrificed during proestrus or estrus. Neither stage of estrous cycle nor adult ovariectomy affected midsagittal CC size. These results provide evidence for organizational effects of ovarian steroids on the female callosum, with the sensitive period of hormone action ending sometime between days 25 and 78.

Animals↗

Developing a quality management program for coded data.

Improving the process of coding data is one important way health information professionals can fulfill their mission of "Quality Healthcare through Quality Information." This article describes principles of continuous quality improvement applied to the coding process.

Abstracting and Indexing↗