Title

Genetic and environmental factors affecting the behavior of ectopic and non-ectopic BXSB mice

Date of Completion

January 1999

Keywords

Biology, Neuroscience|Psychology, Psychobiology

Degree

Ph.D.

Abstract

BXSB/MpJ inbred mice are as a model of developmental dyslexia in large part because approximately 40–60% have neocortical ectopias, an anomaly also found in dyslexics. Ectopias are caused by migration of neurons into the neuron-sparse layer I of cortex. Previous studies have shown that ectopic BXSB mice have superior reference, but inferior working, memory on spatial tasks; and that environmental enrichment can eliminate some of the differences between ectopic and non-ectopic animals. ^ Chapters 2 and 3 further explore the impact of enrichment, through the use of a water version of the Hebb-Williams maze. Ectopics reared in the standard housing condition were better on mazes that favored the use of reference memory, but worse on mazes that favored working memory; whereas subjects raised in the enriched environment showed no differences. A comparison of enriched and standard housing conditions showed that the enriched animals had deficits in working memory, suggesting that the effects of enrichment enhances reference memory at the expense of working memory. ^ In Chapters 4 and 5, the learning behavior of female offspring of two strains of mice consomic for the Y-chromosome, BXSX/MpJ-Yaa (Yaa) and BXSB/MpJ-Yaa+ (Yaa+), was examined. Sires remained with the litters through weaning. Significant differences were found in the Morris water maze and the Lashley III maze, demonstrating that the Y-chromosome plays a role in the development of female behavior. Furthermore, the Y-chromosomes affected ectopics and non-ectopics differently. Since females do not have a Y-chromosome, this effect must be through non-genetic mechanisms. ^ In the second experiment, sires were removed once conception was verified, and the male siblings were removed at birth. Cognitive differences seen in previous Morris maze studies were eliminated. However, females from sires with different Y-chromosomes differed on several measures of affect. These data suggest that the presence of the sire and/or the male offspring postnatally were important in generating the behavioral differences found previously. These data also suggest that the uterine environment plays an important role in affective behavior. Possible mechanisms of Y-chromosome action within the uterine environment, including growth factors and the presence of H-Y antigen, are discussed. ^