Cynthia C. Wimer

Genetic and phenotypic variation in weight of brain and spinal cord between inbred strains of mice.

Abstract Mice of both sexes from 25 inbred strains and 1 distantly related stock were studied for their adult brain weight, spinal cord weight, ratio of brain weight to spinal cord weight, and ratio of brain weight to body weight. Females were significantly greater than males for brain weight, spinal cord weight, and ration of brain weight to body weight. Sizeable strain differences were shown for all traits. The largest coefficients of genetic determination were + 0.62 and + 0.67 for brain weight for males and females, respectively. The two ratios, brain weight to spinal cord weight and brain weight to body weight, were quite different for different strains and showed no correlation between strains. This suggests they are different measures and cannot be considered genetically similar. The weights and volumes of brains were highly correlated.

Three sex dimorphisms in the granule cell layer of the hippocampus in house mice

Inbred strains of mice differ in number of neurons in the dentate granule cell layer of hippocampus and in granule cell density. In a study of both sexes in 6 strains, females had significantly lower granule cell density than males of the same strain. Females of strains with high neuron numbers had significantly fewer granule cells than males of the same strain, while males and females of low neuron number strains did not differ from each other. Sizes of neuronal nuclei were examined in males and females of two strains. No significant strain difference was found, but females had significantly smaller nuclei. The results suggest that hippocampal function is associated with the differing adaptive roles of male and female house mice.

A biometrical-genetic analysis of granule cell number in the area dentata of house mice

Considerable variability in the number of granule cells in the area dentata has been found among inbred strains of mice. In this report a simplified triple-test cross breeding design was employed to identify and discriminate between heritable and non-heritable sources of this variability. Granule cell numbers were estimated in two previously identified extreme strains of mice and in their reciprocal F1 hybrids with 3 strains of mice known to be intermediate between the 2 extremes. Analytical techniques of biometrical genetics applied to the neuron number estimates indicated that genetic transmission of this trait involves genes located upon autosomes. Transmission does not involve cytoplasmic factors within the female egg, or maternally-mediated differences in nutrition. Of the total variability in dentate granule cell number, 86% is estimated to be determined by an additive genetic component. A dorsal-to-ventral increase in the size of granule cell nuclei was found for all genotypes; some possible bases for this increase are discussed.

Genetic variability in forebrain structures between inbred strains of mice

Abstract Brain from males of 9 inbred strains of house mice were examined. Measures used were volume of total brain, absolute and relative volume of neocortex and hippocampus, and cross-sectional area of these structures at several longitudinal sampling points. The results provide evidence for substantial amounts of genetically associated within-species variability, particularly in absolute and relative volume of the structures. Some possible functional implications of this variability were suggested, and it was proposed that this variability might be used experimentally, by employment of genetic selection techniques, to alter the mouse brain systematically.

The genetic organization of neuron number in the granule cell layer of the area dentata in house mice

This report concerns variations in neuron number within the granule cell layer of the area dentata that occur among inbred strains of house mice. There is genetically associated variability in the total number of neurons present, with a very substantial range of estimated values. Systematic strain variations in the orientation of the granule cell layer are also present. When statistical corrections for variations in orientation are made, associations between the neuron numbers of subdivisions of the granule cell layer are consistent with the presence of common genetic determination of neuron number throughout the entire lamina.

Genetic Manipulation of Neuroanatomical Traits

It was probably in 1954 at the Berkeley Faculty Club, around the large table in the middle of the dining room, where there gathered regularly for lunch an exciting conglomeration of individuals representing a variety of academic disciplines, mutually attracted to each other for who knows what reasons, that David Krech held forth on his new research forays into the field of brain chemistry and behavior. Imagine his enthusiasm! … the vast horizons opening up with elucidation of the biochemical basis of behavioral patterns; imagine the responses! … some looking up, others with eyes steadfast on their soup bowls. Probably Everett Dempster from the Department of Genetics at least raised his eyebrows, for his interests were vast and specifically encompassed the question of the extent of genetic variation in the causes of behavioral variation. Krech, persisting, undoubtedly continued telling of Melvin Calvins interest in the problem and the already significant scientific role Edward Bennett was taking in the biochemistry of the visual and somesthetic areas of the rat brain

On the development of strain and sex differences in granule cell number in the area dentata of house mice

Male and female house mice of 6 inbred strains high or low in granule cell number as adults were examined at 3 immature postnatal ages beginning with day 13, and in young adulthood at day 84. The difference between mice of high and of low strains was present by postnatal day 13. Possible contributions of both incremental and decremental developmental events must be considered. Both males and females exhibited a reduction in granule cell number between postnatal days 20 and 27. Competition for efferent target cell sites was considered as a basis for sex-independent granule cell death, but no supporting evidence was obtained. Females displayed a greater reduction in granule cell number than did males. Thus, a sex dimorphism (females lower) appeared at that time. A low-level testosterone effect acting during this period of granule cell death, or a long-term consequence of high perinatal testosterone levels, might be responsible.

On the sources of strain and sex differences in granule cell number in the dentate area of house mice

The origins of strain and sex differences in the number of granule cells in the dentate area of hippocampus were examined in a breeding study employing two inbred strains of mice that differ substantially in granule cell number. Sources of hereditary variation analyzed included autosomes, sex chromosomes, and maternal factors, including cytoplasmic and environmental. The results corroborated those of an earlier study in finding that 80% of the strain variation is attributable to autosomal differences. In addition, there appears to be a cytoplasmic factor that results in a strain-dependent sex dimorphism. The autosomal contribution is attributed to mechanisms operating during the primary phase of granule cell genesis. The possibility that the sex difference results from strain differences in mitochondrial DNA affecting rate of cell death is considered.

The genetic organization of neuron number in the pyramidal cell layer of hippocampal regio superior in house mice.

This report concerns variations in neuron number within the pyramidal cell layer of hippocampal regio superior in 18 inbred strains of house mice. There is a genetically associated variability in the total number of neurons in this pyramidal layer. Systematic strain variations in the orientation of the pyramidal cell layer are also present. Relations between the numbers of neurons in various experimenter-defined subdivisions of regio superior were examined following statistical corrections for the variations in orientation. This led to a preliminary delineation of 4 genetically-defined subdivisions of the regio superior pyramidal cell layer.

A method for estimating nuclear diameter to correct for split nuclei in neuronal counts

A number of methods have been devised for estimating the neuronal population of a brain structure 7. One of the most widely used is the method of counting neuronal nuclei in a sample of sections through the structure. A major source of error in dealing with neuronal count data is the fact that the appearance of a nucleus in more than one section (i.e. split nuclei) will result in overcounting. This error will decrease as the thickness of the section increases in relation to nuclear diameter, but too thick a section will also lead to counting error due to overlapping nuclei. A correction ratio, R, must be calculated such that n, the number of nuclei that should be counted in a section (and not in an adjacent section), is some ratio of no, the number of nuclei actually counted, i.e.