Biomedical subjects

W E Crusio

Publications and source records attributed to W E Crusio.

At least 19 recordsLinked to original sources

PubMed1995

Y chromosomal effects on hippocampal mossy fiber distributions in mice selected for aggression.

The influence of the non-pseudoautosomal region of the Y chromosome (YNPAR) on the sizes of the hippocampal intra- and infrapyramidal mossy fiber (IIPMF) terminal fields were examined in wild house mice. For this purpose selection lines for short attack latency (SAL), long attack latency (LAL), and their respective congenics for the YNPAR were used. We found an incremental effect of the (non-aggressive) LAL YNPAR, combined with an additive effect of the line background on the sizes of the IIPMF terminal fields. In contrast, only the line background affected attack latency. The implications of this finding for the previously observed correlation between the size of the IIPMF and aggression in male house mice are discussed.

Aggression↗

PubMed1995

Organization of motor and posture patterns in paradise fish (Macropodus opercularis): environmental and genetic components of phenotypical correlation structures.

Paradise fish exhibit complex, environment-specific behavioral responses which consist of behavioral elements (motor and posture patterns) appearing in a typical, correlated manner. The genetic and environmental components underlying these phenotypical correlations have not been comprehensively investigated. Therefore, we have analyzed the behavioral elements of paradise fish from the nine populations of a 3 x 3 full diallel cross by employing a bivariate extension of the Hayman-Jinks variance-covariance analysis, demonstrating the presence of significant environmental and genetic correlations. To investigate the multivariate structure of the correlation matrices obtained, we subjected the phenotypical, environmental, additive genetic, and dominance correlations to principal-component analyses (PCAs). After rotation, the phenotypical principal factor pattern found was similar to previously obtained ones, suggesting stable underlying biological mechanisms. The environmental PCA extracted several environmental principal factors that were highly situation-specific. PCAs of the matrices of genetic correlations extracted only a small number of genetic principal factors which were not situation-specific, suggesting a relatively simple underlying genetic structure.

Animals↗

PubMed1995

Correlations between radial-maze learning and structural variations of septum and hippocampus in rodents.

Large, but non-pathological, individual differences in neuroanatomy of the brain exist in rodents, which have been shown to covary with behavioral traits. In the present review, we explore the relationship between variations in the extent of the intra- and infrapyramidal mossy fiber projection of the hippocampus and spatial and non-spatial learning capacities in mice and rats. Preliminary data concerning anatomical variation in the septo-hippocampal cholinergic system and its consequences for individual behavior are also presented. We conclude that the hippocampal intra- and infrapyramidal mossy fiber projection is intimately involved in the regulation of spatial, but not of non-spatial learning capabilities. Although lesion studies have shown that a well-functioning cholinergic system is a prerequisite for performance in spatial learning tasks, our preliminary data suggest that individual differences in the cholinergic system do not explain individual differences in learning.

Animals↗

PubMed1991

Spatial and non-spatial spontaneous alternation and hippocampal mossy fibre distribution in nine inbred mouse strains.

Ten male mice from each one of nine inbred strains were tested for spontaneous alternation in a T-maze, which was placed in a spatially richly structured room. Each test consisted of two trials, the first choice to be made was forced, the second one free. By turning the maze 180 degrees between choices during 8 of the 16 tests, 3 variables could be measured: total alternation, spatial alternation, and non-spatial alternation. After Timm's staining, the sizes of the intra- and infrapyramidal mossy fibre terminal fields (iip-MF) were measured. Significant strain differences were found for all variables, but none of the behavioural variables correlated with hippocampal variation. These results disagree with earlier experiments, where large correlations between the iip-MF and spatial working memory were found. Some hypotheses to explain this discrepancy are presented.

Animals↗

PubMed1991

A genetic-correlational study of hippocampal structural variation and variation in exploratory activities of mice.

Our previous work provided evidence that hippocampal opioid peptides form an important neurochemical substrate underlying the gene-dependent exploratory behavior of mice. A prominent hippocampal opioid is dynorphin B, which resides in the mossy fibers exclusively. In order to seek support for causal relationships between dynorphinergic hippocampal mechanisms and exploration, a quantitative-genetic method was chosen. For this purpose, mice from the inbred strains C57BL/6, DBA/2, BLN, and CPB-K were used. Their hippocampal mossy fiber projections were visualized by means of immunohistochemistry, using a highly specific anti-dynorphin B antiserum. The additive-genetic correlations that were estimated suggest pleiotropic gene effects on locomotion, rearing-up, wall-leaning, and several intra- and infrapyramidal mossy fiber (iipMF) variables. Long iipMF, in particular, were found to be associated with high exploratory activity.

Animals↗

PubMed1991

A genetic-correlational study of hippocampal neurochemical variation and variation in exploratory activities of mice.

Previously, we have demonstrated that hippocampal mossy fibers, containing the opioid peptide dynorphin B, are functionally connected with the gene-dependent exploratory behavior of mice. In order to seek further evidence of causal relationships between dynorphin B action and exploration, a quantitative-genetic method was chosen. For this purpose, mice from the inbred strains C57BL/6, DBA/2, BLN, and CPB-K were used. By means of radioimmunoassay, the hippocampal level of dynorphin B was monitored in mice that had been exposed to environmental novelty, as compared to naive animals. Clear evidence was obtained that novelty induces the release of hippocampal dynorphin B. Furthermore, low tissue content was found to be causally connected with high exploratory scores.

Animals↗

PubMed1991

Behavioural and neuroanatomical divergence between two sublines of C57BL/6J inbred mice.

Male mice of strains C57BL/6J and DBA/2J differ reproducibly in a number of behaviours displayed in an open-field. In particular, C57BL/6J mice show a higher rearing-up frequency than do DBA/2J animals. Recently, a marked drop occurred in the frequency with which this behaviour is displayed by the C57BL/6J//Nmg (N) subline, that has been separated from the original C57BL/6J line over 62 generations. Comparison of our animals with the C57BL/6J//Kun(K) subline, separated from the Jackson parent over at least 40 generations, showed a significant strain difference for rearing. Since both a positive additive-genetic correlation between rearing and the size of the intra- and infrapyramidal mossy fibre terminal field (iipMF) and a correlated response in the size of the iipMF to selection for rearing have been found previously, we expected to find smaller iipMF in N, as compared with K. After processing for Timm's stain, this predicted difference was indeed found. Skin grafting demonstrated that the two sublines were still completely histocompatible, excluding a possible genetic contamination of N. This provides very strong support for the hypothesis that both the behavioural and the neuroanatomical differences between these sublines are caused by a single spontaneous mutation in the N line and strengthens the idea of a functional relationship between the structural and the behavioural variable.

Animals↗

PubMed1991

Early postnatal hyperthyroidism improves both working and reference memory in a spatial radial-maze task in adult mice.

Newborn male pups of the inbred mouse strain DBA/2J were injected with a buffered solution of L-thyroxine, known to induce a hyperplasia of the intra- and infrapyramidal mossy fiber terminal fields (iip-MF). Because previous studies have shown that the size of the iip-MF correlates positively with both reference memory and working memory in a spatial radial maze task, we expected improved performance on such a task in the treated animals. Such an improvement was in fact found for both reference and working memory. We conclude that the iip-MF are functionally involved in the regulation of spatial learning and memory in mice.

Animals↗

PubMed1991

Early postnatal hyperthyroidism alters hippocampal circuitry and improves radial-maze learning in adult mice.

Inbred mice show strain-specific differences in the hippocampal mossy fiber projection. These differences are most pronounced in the portion of the projection that forms synaptic connections with the basal dendrites of the CA3 pyramidal neurons [intra- and infrapyramidal mossy fiber (IIP-MF) projection]. We have previously demonstrated that the extent of the IIP-MF subfield is positively correlated with the capacity to perform a spatial radial-maze task and that an experimentally induced enlargement of the IIP-MFs, by means of postnatal thyroxine treatment, predicted the ability of adult two-way avoidance learning. In the present study, we tested whether this treatment would also influence radial-maze performance. Forty-five male mouse pups from the inbred strain DBA/2 (chosen because of scanty IIP-MF projection and poor radial-maze learning) were divided into three groups that received daily injections of either 2 micrograms L-thyroxine, an alkaline vehicle solution, or physiological saline. Treatment lasted from postnatal days 0 to 11. At the age of 3 months, these animals were tested in an eight-arm radial maze. The extent of their IIP-MF projections was measured by means of planimetry on Timm-stained sections. Thyroxine-treated animals made significantly fewer errors and had larger IIP-MF projections as compared to both control groups. Within each group, the individual variability of the IIP-MF projection was significantly and positively correlated with performance. We conclude that experimentally modified IIP-MF projections mediate processes underlying spatial working memory. It would appear that the hippocampal circuitry alterations induced by postnatal hyperthyroidism can counteract a hereditary lack of talent, albeit only partially and in selected populations.

Animals↗

PubMed1990

No correlations between spatial and non-spatial reference memory in a T-maze task and hippocampal mossy fibre distribution in the mouse.

Two reference memory tasks were tested in a T-maze, which was placed in a spatially richly structured environment and turned 180 degrees between trials following a semi-random schedule. Male mice from 9 different inbred strains were either trained always to go to the same place (spatial task) or always to make the same turn (non-spatial task). Animals were subsequently processed for Timm's stain and the sizes of their intra- and infrahippocampal mossy fibre terminal fields (ipp-MF) were measured. Significant strain differences were found for this variable and in both learning tasks, but learning and hippocampal variation did not correlate. This disagrees with earlier findings in a radial maze, where significant correlations between the iipMF and spatial reference memory were obtained. Two hypotheses are brought forward to explain this discrepancy. First, in radial mazes (multiple choices) different memory capabilities might be used than in T-mazes (only two choices). Second, a considerable amount of stress appeared to be present in our subjects, possibly induced by the large size of the T-maze. This might have interfered negatively with acquisition. Further experiments will be needed to test these hypotheses.

Animals↗

PubMed1990

A multivariate morphometric analysis of hippocampal anatomical variation in C57BL/6 in equilibrium BALB/c chimeric mice.

We investigated hippocampal anatomy in artificially-produced chimeras derived by the aggregation of embryos from two widely-studied inbred mouse strains, C57BL/6J and BALB/cJ. Contrary to expectations, the chimeras were not always intermediate between the parental strains. For a number of characters, the chimeras exceeded qualitatively as well as quantitatively the phenotypical range displayed by both inbred parental strains. These findings imply that if only one parent is available for comparison, for instance, in studies involving a normally inviable genotype, separating effects of this genotype from idiosyncratic effects inherent to the chimeric model will be very difficult, if not impossible.

Animals↗

PubMed1990

Selective advantage of fra (X) heterozygotes.

The high incidence of the fra (X) syndrome (about 1:2000 male newborns) requires an explanation in view of the low fitness of mentally retarded hemizygous males and heterozygous females. In the past, it has been proposed that the mutation rate may be unusually high, and that mutations occur exclusively in male germ cells. According to an alternative hypothesis, a moderately high mutation rate might combine with a selective advantage of clinically unaffected heterozygotes. In earlier studies, such a combined hypothesis was shown to lead to plausible implications regarding mutation rate and fitness. Moreover, a mutation rate in male germ cells of the magnitude required by the exclusive mutation hypothesis was excluded by studies on comprehensive pedigree data. In this third study in the series, an increased fitness of heterozygous females is demonstrated directly by a comparison of the reproductive performance of heterozygotes with that of adequate controls (mothers and grandparents of Down's syndrome patients). Since, average numbers of children have decreased during recent decades in populations of industrialized countries, heterozygotes (mothers of affected probands and their female relatives in their own generation) were subdivided into those born before and after 1940. Moreover, sibship sizes of probands' mothers and fathers were analyzed separately for family branches in which the fra (X) trait segregated (mostly the maternal branch), or did not segregate (in most instances the paternal branch). In all four categories reproductive performance in heterozygotes was found to be higher than in the controls. This difference was significant statistically for two of the four groups; it was small and nonsignificant only for the parental family branch in which the fra (X) mutant did not segregate and for mothers born after 1940. Fitness estimates ranged between 1.11 and 1.36. A higher incidence of dizygotic twinning suggests a biological component for this increased fertility. On the other hand, fra (X) families have a significantly lower social status than the controls. This suggests a socio-psychological component of their higher fertility. Apparently, both components contribute to their fertility; at present, their relative importance cannot be assessed.

Birth Rate↗

PubMed1990

Inheritance of species-specific behaviors in the paradise fish (Macropodus opercularis): a diallel study.

Species-specific elements of the paradise fish's ethogram were recorded in one familiar and three different unfamiliar environments, which were designed to model certain features of this species' natural habitat: (1) a densely vegetated home range, (2) a novel open field, (3) a small novel place, and (4) a small novel place with a predator. The inheritance of the behavioral elements was investigated employing a five-times-replicated diallel cross among three inbred strains. A detailed Hayman analysis of variance and a variance-covariance analysis were performed to uncover the genetic architectures of these phenotypes. Additive genetic effects and/or ambidirectional dominance was found to be characteristic of most species-specific behavioral elements studied, suggesting an evolutionary history of stabilizing selection.

Animals↗

PubMed1990

Hippocampal mossy fibers and radial-maze learning in the mouse: a correlation with spatial working memory but not with non-spatial reference memory.

One hundred and eight male mice from nine different inbred strains were tested for two aspects of learning in an eight-arm radial maze. In the first experimental arrangement of the maze, measuring spatial working memory, clear strain differences were found on the fifth day of training. Furthermore, this type of learning showed a high positive correlation with the size of the intra- and infrapyramidal hippocampal mossy fiber terminal field as revealed with Timm's staining. In the second experiment, in which non-spatial reference memory was tested, significant strain differences were found for the learning variables, but there were no significant covariations with the sizes of the intra- and infrapyramidal mossy fiber terminal fields. These results, combined with previous data, suggest that heritable variations of the hippocampal intra- and infrapyramidal mossy fiber projection influence processes determining spatial learning capabilities in mice.

Animals↗

PubMed1989

Using genetically-defined rodent strains for the identification of hippocampal traits relevant for two-way avoidance behavior: a non-invasive approach.

Genetically-defined rodent strains permit the identification of hippocampal traits which are of functional relevance for the performance of two-way avoidance behavior. This is exemplified here by analyzing the relationship between infrapyramidal mossy fibers (a tiny projection terminating upon the basal dendrites of hippocampal pyramidal neurons) and two-way avoidance learning in about 800 animals. The necessary steps include 1) identification of structural traits sensitive to selective breeding for extremes in two-way avoidance, 2) testing the robustness of the associations found by studying individual and genetical correlations between hippocampal traits and behavior, 3) establishing causal relationships by Mendelian crossing of strains with extreme structural traits and studying the behavioral consequences of such structural 'randomization', 4) confirming causal relationships by manipulating the structural variable in inbred (isogenic) strains, thereby eliminating the possibility of genetic linkage, and 5) ruling out the possibility of spurious associations by studying the correlations between the hippocampal trait and other behaviors known to depend on hippocampal functioning. In comparison with the classical lesion approach for identifying relationships between brain and behavior, the present procedure appears to be superior in two aspects: it is non-invasive, and it focuses automatically on those brain traits which are used by natural selection to shape behaviorally-defined animal populations, i.e., it reveals the natural regulators of behavior.

Animals↗

PubMed1989

Behavioral responses to novelty and structural variation of the hippocampus in mice. I. Quantitative-genetic analysis of behavior in the open-field.

As a first step towards a multivariate quantitative-genetic analysis of covariations between heritable variation in hippocampal structure and mouse behavior, a univariate analysis of the genetic architecture of behavioral responses to novelty is presented. For several components of exploratory behavior considerable amounts of genetic variation were found and an evolutionary history of stabilizing selection for intermediate levels of exploration was inferred. Comparison of these results with those from a previous study indicated that even a relatively small diallel cross, involving 4-5 inbred strains, may provide useful genetic information on a specific sample of animals. Larger numbers of strains are needed to provide precise estimates of genetic parameters in a population.

Animals↗

PubMed1989

Behavioral responses to novelty and structural variation of the hippocampus in mice. II. Multivariate genetic analysis.

On the basis of results from lesion studies in rodents, covariations are expected to exist between naturally-occurring heritable variations in hippocampal morphology and exploratory behavior elicited by novel surroundings. For this reason, we set up a full diallel cross between five inbred mouse strains and analyzed the behavioral and the hippocampal anatomical variation in male animals from this cross. Employing a bivariate extension of the diallel-cross analysis, estimates were obtained for the phenotypical, environmental, and genetical correlations between the phenotypes studied. A factor analysis performed on the matrix of additive-genetic correlations revealed that variations in the size of the intra- and infrapyramidal mossy fiber terminal fields (iip-MF) are negatively related to open-field exploration and novelty-induced fear. These results indicate that having larger iip-MF projections promotes the collection and processing of information about a novel environment, entailing lower levels of exploration and fear.

Animals↗

PubMed1989

Y-chromosomal effects on discrimination learning and hippocampal asymmetry in mice.

From a four-way cross between unrelated inbred strains of mice, a random-breeding line was developed that segregated at two coat-color loci and carried Y chromosomes from different sources. Adult males were used for measurements of black-white discrimination learning and 7-day response retention in a water maze, body weight, brain weight, and left- and right-side hippocampus weight. Clear evidence was obtained of Y-linked influences on response acquisition, body weight, right-side hippocampus weight, and hippocampal asymmetry, whereas direct effects of autosome 9 were indicated with regard to right-side hippocampus weight only. However, epistatic interactions of the Y chromosome with autosome 9 were found for response acquisition and body weight and with autosome 4 for hippocampal asymmetry.

Animals↗