Biomedical subjects

N S Waters

Publications and source records attributed to N S Waters.

17 recordsLinked to original sources

PubMed2000

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↗

PubMed1997

Insensitivity of the hippocampus to environmental stimulation during postnatal development.

Development of cortical sensory systems is influenced by environmental experience during "sensitive periods," before onset of behavioral function. During these periods, synaptic plasticity is observed, and neuronal function shows increased responsiveness to environmental stimulation. Because the hippocampus is late to develop, and because it demonstrates synaptic plasticity before the onset of behavioral function, this experiment was designed to determine whether, like the sensory cortices, the hippocampus undergoes a period of enhanced responsiveness to the environment. Rats at three ages [postnatal day 16 (P16), P23, and P30] were tested on a hippocampally dependent task, spontaneous alternation, and exposed to a novel environment. They were then killed and processed for immunocytochemistry to Fos or for in vitro electrophysiology in hippocampal area CA1. Age-matched control subjects were killed immediately after removal from the home cage. Spontaneous alternation was only observed in the oldest (P30) animals. In these same animals, the environmental manipulation resulted in an increase in Fos-like immunoreactivity (FL-IR), relative to controls, and a decrease in the ability to induce long-term potentiation (LTP). In P16 and P23 animals, the environmental manipulation resulted in no differences in hippocampal FL-IR or LTP. These results suggest that, rather than showing increased responsiveness to the environment at these ages, the hippocampus is environmentally insensitive and that it is isolated from the effects of environmental stimuli. The hippocampus, a neural region important for higher cognitive function, may develop via a mechanism different from those observed in the primary sensory cortices.

Aging↗

PubMed1997

Manipulation of behavioral disorders in autoimmune mice via prolactin.

Autoimmune mice perform poorly in two-way active avoidance tasks, and the extent of this performance deficit appears to be related to the extent of autoimmunity following developmental manipulations. In the current study, the pituitary hormone prolactin, which has immune-enhancing effects, was used to manipulate this behavioral disorder in adulthood. Prolatinergic manipulation may be achieved by the use of dopaminergic drugs. In two experiments, autoimmune NZB X NZW F1 (BW) mice received either pimozide (PIM; a D2 antagonist) or bromocriptine (CB154; a dopamine agonist) in their drinking water. Control subjects received plain water. Following treatment, subjects were tested in an activity monitor, and active avoidance learning. Circulating PRL levels, as measured by RIA, were significantly increased by PIM and significantly decreased by CB154. Neither drug affected circulating levels of autoantibodies to DNA or cardiolipin, a phospholipid. In Experiment 1, in which mice were tested at 12 weeks of age, after 6 weeks of drug treatment, PIM treated animals of both sexes showed significantly more failures to escape the shock in avoidance conditioning, while CB154 did not have significant effects. In Experiment 2, in which mice were tested at 16 weeks of age, after 12 weeks of drug treatment, CB154 treated females (males were not tested) showed significantly fewer failures to escape, while PIM did not have significant effects. The effects of PRL on behavior, and its relation to immune system function, are discussed.

Animals↗

PubMed1997

Effects of cortical ectopias on spatial delayed-matching-to-sample performance in BXSB mice.

BXSB mice have small neocortical anomalies (ectopic collections of neurons in layer I), with an incidence of about 40-60%. Previous studies have found that ectopic mice from this strain are faster than non-ectopics in learning the Morris water maze (reference memory), but have poorer working memory for spatial learning. The current study continues the investigation of working memory by testing ectopic and non-ectopic BXSB mice on a spatial delayed-matching-to-sample test (S-DMTS; also called spatial learning sets or 'working memory' water maze). In this test, the mice must find a submerged platform in a pool of water. The platform changes location with every problem, or block of four trials. The subject has 'matched to sample' if it locates the platform in less time on the second trial of each problem than it did on the first. Of 33 subjects, 8 had cortical ectopias, one had a small neuron-free gliotic area, and 24 were normal. The normal subjects showed a decrease in time to escape over the first 2 trials of the first 5 problems, while the ectopic subjects did not show a decrease until the third trial, indicating that ectopic mice required more trials to put the platform location into working memory. The site of the ectopias is prefrontal/motor cortex, and we hypothesize that is the cause of the poorer working memory.

Animals↗

PubMed1996

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↗

PubMed1996

Differential prolactin responsiveness to stress in left- and right-pawed mice.

Behavioral laterality has been shown to be related to immunological and endocrinological responsiveness in mice. The current study extended these findings by examining the pituitary hormone prolactin, and its response to stress, in left- and right-pawed mice. In two experiments, mice were tested on two measures of behavioral laterality, the Collins paw preference test and the Lateral Paw Preference (LPP) test. Circulating PRL levels were then measured in all subjects under baseline and stressed conditions. In Experiment 1, the PRL stress response was related to Collins paw preference in interaction with coat-color among females of a genetically heterogeneous group. Left-pawed black females showed a significant increase in PRL, while right-pawed black females did not. Among agouti mice, left-pawed females showed a significant decrease, while right-pawed did not. Experiment 2 used a genetically homogeneous group of agouti C3H mice. Again there were effects of Collins paw preference among females, with the right-pawed showing a significant increase in PRL following stress. In neither experiment were there effects of LPP. In neither experiment were there lateralized differences among males. These results indicate lateralized regulation of PRL among females, similar to that previously observed for ACTH regulation.

Animals↗

PubMed1996

Effects of embryo transfer and cortical ectopias upon the behavior of BXSB-Yaa and BXSB-Yaa + mice.

The BXSB-Yaa and BXSB-Yaa + inbred strains of mice differ primarily with respect to the Y chromosome, although there is evidence that they differ on several autosomal genes as well. Each strain has ectopic collections of neurons in neocortical layer I (ectopias), with a higher occurrence in males (58%) than females (42%). Conventionally reared mice from these strains were compared to mice that were transferred, as 8-cell embryos, into the uteri of non-autoimmune recipients, who gave birth to and reared the offspring. The transfer procedure did not change the incidence of ectopias in either sex. There were, however, major differences in behavior. Compared to conventionally reared controls, embryo transfer mice had greater behavioral asymmetry, poorer performance in a black-white discrimination, poorer Morris maze learning, better Lashley maze learning, and better performance in a two-way shuttlebox. Within the transfer groups, females differed as much as males, confirming our prior findings and supporting our thesis that the two strains differ on several autosomal genes in addition to the Y chromosome. These findings show that the intra-uterine environment can powerfully and selectively affect later behavior. When ectopic and non-ectopic mice were compared, BXSB-Yaa mice with neocortical ectopias were better able to learn the Morris spatial maze than non-ectopic controls; this was true whether the mice were conventionally reared or embryo transferred. In contrast, BXSB-Yaa + ectopic mice did not differ from their controls if conventionally reared, but were much worse than controls if embryo transferred.

Animals↗

PubMed1995

Behavioral consequences of neonatal injury of the neocortex.

Several strains of autoimmune mice spontaneously develop molecular layer ectopias that are similar in appearance to those seen in humans and are caused by disturbances in neocortical neuronal migration. These mice also exhibit behavioral anomalies, some of which correlate with ectopias, others with the immunological disorder. In this study, we induced neocortical ectopias (via puncture wounds) and microgyria (via freezing lesions) in the neocortex of 1-day-old (newborn) mice without immune disorders in an attempt to further disentangle the effects of autoimmunity and of cortical malformation on behavior. In addition, we wished to compare the behavioral effects of small ectopias to larger microgyric lesions. DBA mice were assigned at birth to receive either a puncture wound or freezing lesion of either the left or right hemisphere. An independent group was subjected to sham surgery. In adulthood, these mice were given a battery of tests designed to measure lateralization and learning capacity. Lesioned mice (irrespective of hemisphere or type of damage) performed poorly when compared to sham-operated animals in discrimination learning, in a spatial Morris Maze Match-to-Sample task, and in a Lashley Type III maze. In shuttlebox avoidance conditioning, where immunological disorder has been shown to compromise behavioral performance in autoimmune mice, there was no difference between lesioned and sham animals. These results (1) support the dissociation between the effects of developmental neocortical anomalies and autoimmune disease on behavior (2) reveal similarities between spontaneous and induced neocortical malformations and (3) fail to support a difference in behavioral effects between ectopias and microgyria.

Animals↗

PubMed1994

Analysis of two measures of paw preference in a large population of inbred mice.

Two measures of lateralized forelimb usage, the Collins paw preference test and the Lateral Paw Preference test (LPP), were tested in 693 mice of 29 inbred strains and F1 crosses, and 2 embryo transfer groups. These strains included NZB, SM, and the NXSM recombinant inbred (RI) strains; RF and the NXRF RI strains; BXSB and the Y-consomic BXSB-Yaa+; DBA/2 and F1s of DBA/2 and BXSB and BXSB-Yaa; and NZB x NZW F1s. The findings indicated that (1) the Collins and LPP tests were independent in terms of direction of lateralization, (2) there were significant population biases of 60.96% rightward on the LPP test, and 54.39% leftward on the Collins test, (3) there were significant strain differences on measures of absolute asymmetry on both tests, (4) there were strain differences for direction of asymmetry on the Collins test, but not on LPP, (5) on the basis of the NXSM RI strains, 3 genetic loci contribute to strength of laterality on the LPP test, and (6) there was a strong correlation among strain means for strength of lateralization on the two tests. These results extend previous findings on the strength and direction of laterality, showing that two independent systems for direction of laterality may depend on the same mechanism for magnitude, and establish that multiple factors of handedness, previously identified in humans and other primates, also exist in mice.

Animals↗

PubMed1993

Behavior, cortical ectopias, and autoimmunity in BXSB-Yaa and BXSB-Yaa+ mice.

The BXSB-Yaa recombinant inbred strain was created by crossing a male SB/Le with a female C57BL/6J. A Y chromosome factor derived from the SB/Le male, known as the autoimmune accelerator (Yaa), leads to an earlier onset and greater severity of autoimmune disease in males. In contrast, male BXSB mice, which lack the Yaa gene (called BXSB-Yaa+) because their Y chromosome is derived from the C57BL/6J, do not develop an autoimmune condition. To examine the influence of the Y chromosome on behavior, cortical ectopia incidence, and immune functioning, males and females of these two strains were compared. Significant strain differences (for both sexes) were found for behavioral measures including discrimination, spatial and avoidance learning, and activity. For immunological parameters, a sex difference was seen in the BXSB-Yaa (males more autoimmune), but not in the BXSB-Yaa+ strain. As expected, male BXSB-Yaas were more autoimmune than male BXSB-Yaa+s. However, there was also a strain difference for IgG in the females (BXSB-Yaa+ greater). No strain difference was found for the presence of ectopias. However, there was a sex difference across both strains, with males having a higher incidence. BXSB-Yaa and BXSB-Yaa+ mice have behavioral and immunological differences greater than would be predicted by their known genetic differences. The significant differences between the two female groups suggest that the two strains differ with respect to autosomal genes, in addition to the Y chromosome. The incidence of ectopias is independent of this genetic difference and is influenced by the subject's sex.

Animals↗

PubMed1992

Environmental enrichment, neocortical ectopias, and behavior in the autoimmune NZB mouse.

New Zealand Black (NZB) mice have severe autoimmune disease and approximately 40% have cortical ectopias in layer I of sensorimotor cortex. Because the ectopias are similar to those found in dyslexics, NZB mice have been used as an animal model for developmental learning disorders. In addition, these mice have been used as a model of learning deficits associated with autoimmune disease. To determine whether early intervention would affect learning processes in NZB mice, they were reared after weaning in standard cages or enriched environments. They were given a battery of behavioral tests to measure learning, laterality, and activity, after which they were sacrificed and their brains examined for cortical ectopias. The tests sorted into two behavioral sets. Ectopia-associated behaviors included black-white discrimination learning and the Morris spatial maze. As a group, the mice performed well on these tasks. Ectopic mice had poorer performance than non-ectopics on these measures, and environmental enrichment countered the effects of the ectopias. Autoimmune-associated behavior involved two-way avoidance learning in a shuttlebox. Mice were uniformely poor on this task, ectopias did not affect behavior, and environmental enrichment was without benefit. Evidence from this and other studies shows that poor shuttlebox performance is related to the presence of autoimmune disease. Thus, autoimmune disease and cortical ectopias each appear to affect a separate set of behavioral processes. Environmental enrichment is most effective for behavioral impairments mediated via cortical ectopias, but is much less effective, if at all, if autoimmunity is the primary mediator of the impairments.

Animals↗

PubMed1992

Behavior, ectopias and immunity in BD/DB reciprocal crosses.

In a previous study, in which fertilized DBA ova were transferred into an autoimmune female, and NZB ova were transferred into a non-autoimmune female, we found that (1) the maternal environment affected the degree of autoimmunity, (2) the incidence of cortical ectopias was not affected by the maternal environment (3) DBA and NZB females had greater paw asymmetry if reared in an autoimmune uterus, and (4) avoidance learning scores were inversely related to degree of autoimmunity. In the present experiment, reciprocal crosses of DBA and BXSB mice were studied to confirm and extend the original findings. DB mice (DBA female x BXSB male) had greater immune activity than the BD animals, had poorer avoidance learning, but were better on black-white discrimination learning and the Lashley III maze. The BD mice had greater paw asymmetry. Only one of 38 animals had a cortical ectopia. The results lead to the following conclusions: (1) there is an inverse relationship between amount of immune activity and active avoidance learning; (2) some uterine factor in autoimmune mice causes females to have greater paw asymmetry; (3) cortical ectopias are under genetic control; and (4) the lesser immune activity of the BD mice suggests that they developed a suppressor system following early exposure to autoimmunity in the uterine/maternal environment.

Animals↗

PubMed1991

Effects of the autoimmune uterine/maternal environment upon cortical ectopias, behavior and autoimmunity.

NZB and BXSB mice develop autoimmune disease and learn poorly on avoidance tasks. In addition, many of these mice have ectopic collections of neurons, which occur prenatally, in layer I of the cerebral neocortex. The purpose of these experiments was to evaluate the contribution of the uterine/maternal environment upon these variables by transferring fertilized ova to an autoimmune or a non-autoimmune maternal host. In Experiment 1 fertilized DBA ova were transferred into the uteri of BXSB maternal recipients. Later, these animals and conventionally reared DBAs were tested for paw preference, swimming rotation, water escape learning, and shuttlebox avoidance learning. Blood was taken for measurement of immune parameters, and their brains were examined for cortical ectopias. As compared to conventional DBAs, the ova transfer mice had greater amounts of anti-dsDNA autoantibodies, poorer avoidance learning, and poorer water escape learning; in addition, the females had greater paw asymmetry. There was only 1 ectopia in the 81 ova transfer animals, and none in the 78 control mice. In Experiment 2 fertilized NZB ova were transferred into the uteri of non-autoimmune hybrid females and the same procedures were followed as in Experiment 1. Ova transfer mice had lesser amounts of anti-dsDNA autoantibodies, better avoidance learning scores, and females had less paw asymmetry; in addition, within the ova transfer group males were clockwise swimmers whereas females swam counterclockwise. There were 4 ectopics out of 17 ova transfer mice (23.5%), which did not differ from the 40.5% of the control group. In both experiments the uterine environment did not affect the occurrence of ectopias.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

A measure of lateral paw preference in the mouse.

A lateral paw preference testing unit is described. Mice are allowed access to preferred food with either their left or right forepaw, and the amount eaten with each paw is measured. The unit allows easy measurement and quantification of this behavior, without requiring food deprivation or continuous monitoring of the subjects, and may be performed in the subject's home cage. Its reliability under a number of conditions is reported. The results do not correlate with those obtained using the Collins paw preference test.

Animals↗

PubMed1991

Corpus callosum: interactive effects of infantile handling and testosterone in the rat.

Previous research found that the corpus callosum of male rats is larger than that of females; handling rats in infancy enhances this sex difference; and female rat pups, when handled in infancy and given 1 injection of testosterone propionate (TP) on Day 4 of life, will have callosa as large as those of males. In 2 experiments, male pups were castrated on Day 1 or received sham surgery; female pups were injected with TP on Day 4 or received an oil injection. Litters were handled or nonhandled. The previous finding that females, when handled and given TP in infancy, have a larger callosum was confirmed; however, a TP effect when administered to nonhandled females was not found. Because handling is known to cause a corticosterone release, these findings were interpreted as evidence of a developmental interaction between adrenal and gonadal hormones at the cortical level.

Animals↗

PubMed1990

A computer-aided procedure for measuring swim rotation.

As a rat or mouse swims in a small cylinder, its movements are tracked by an observer using a joystick, and the information is sent to a Macintosh computer. The swimming circle is broken into quadrants. The sequence of quadrants entered and the time spent in each quadrant are recorded as the basic data. From the data set one can extract full or partial turns, clockwise or counterclockwise rotations, total activity, and speed of swimming clockwise and counterclockwise. Two laterality indices, one based on full turns and the other on partial turns, are calculated. Test-retest reliability for rats and mice for 3-minute and 5-minute observation intervals are reported.

Animals↗

PubMed1990

A computer-aided procedure for measuring Morris maze performance.

A common procedure for recording Morris maze performance is to trace the animal's path on a template of the maze. This procedure is used in a computer-based recording system. A maze template is placed on a digitizing tablet, an electronic cursor with pen attachment is used to trace the animal's path, and the data are sent to a computer where a program called Spatial Maze obtains the following measurements: total time in seconds, total distance traveled in inches, average speed, absolute and percent time in each quadrant, absolute and percent time in each annulus, the XY coordinate information needed to reconstruct the complete path of the animal, swimming angles, and the number of rears while on the platform. These measurements are then sent to Excel for statistical and graphic analyses.

Animals↗