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Biomedical subjects

W E Crusio

Publications and source records attributed to W E Crusio.

At least 19 recordsLinked to original sources
PubMed2004

A note on the effect of within-strain sample sizes on QTL mapping in recombinant inbred strain studies.

This note explores the effect of within-strain sample sizes on the correlations between a phenotype and a molecular-genetic marker in a battery of inbred strains. It is shown that the maximum correlation possible between a molecular marker and a behavioral or neuronal phenotype equals the additive-genetic correlation. How close the strain correlation will approach the additive-genetic correlation depends only on heritability and within-strain sample sizes. The equations derived can be used to optimize designs of studies attempting to localize Quantitative Trait Loci utilizing Recombinant Inbred Strains, provided information about the heritability of the character under study is available.

Animals↗
PubMed2001

Genetic dissection of mouse exploratory behaviour.

A large variety of apparatus and procedures are being employed to measure mouse exploratory behaviour. Definitions of what constitutes exploration also vary widely. The present article reviews two studies whose results permit a genetic dissection of behaviour displayed in an open-field situation. The results agree that factors representing exploration and stress/fear underlie this type of behaviour. Both factors appear to be linked to neuroanatomical variation in the sizes of the hippocampal intra- and infrapyramidal mossy fibre terminal fields. Multivariate analysis of genetic correlations may render important insights into the structure of behaviour and its relations with neuroanatomical and neurophysiological systems.

Animals↗
PubMed2001

Neuroanatomy of cerebellum and olfactory bulb in a substrain of C57BL/6J inbred mice carrying a spontaneous mutation.

Mice of the inbred C57BL/6JNmg substrain carry a mutation decreasing the size of the zinc-rich hippocampal intra- and infrapyramidal mossy fibre (IIPMF) terminal fields. In the present experiment, it was investigated whether this neurological mutation has also effects on other characteristics of the brain. No morphological differences were found in two other laminated neural structures, the olfactory bulb, where the accessory granular layer is also rich in zinc terminals, and the cerebellum. However, the mutants had a somewhat inferior performance on a motor function task known to test cerebellar involvement. The present findings confirm that previously found effects of this mutation on different types of behaviour are most probably due to the IIPMF. These substrains provide a powerful tool to localise the gene involved and subsequently investigate the plausible pathways leading from gene to behaviour.

Animals↗
PubMed2000

Water maze and radial maze learning and the density of binding sites of glutamate, GABA, and serotonin receptors in the hippocampus of inbred mouse strains.

Correlations between the densities of ionotropic glutamate, GABA(A), and serotonin binding sites in the hippocampus of seven inbred mouse strains and strain-specific learning capacities in two types of maze were studied. Binding site densities were measured with quantitative receptor autoradiography. Learning capacities were determined in a water maze task as well as in spatial and nonspatial versions of an eight-arm radial maze. The densities of most binding sites differed significantly between the strains in the subfields of Ammon's horn (CA1 and CA3) and the dentate gyrus, except for serotonin binding sites in CA1. By comparing the different strains, significant receptor-behavioral correlations between the densities of the GABA(A) receptors and the activity-dependent behavior in the water maze as well as the spatial learning in the radial maze were found. The densities of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionate (AMPA) and kainate receptors correlated positively with learning capacity in the spatial eight-arm radial maze. We conclude that hereditary variations mainly in AMPA, kainate, and GABA(A) receptor densities are involved in behavioral variations in spatial and nonspatial learning tasks.

Analysis of Variance↗
PubMed2000

Divergent levels of anxiety in mice selected for differences in sensitivity to a convulsant agent.

Spontaneous behavior patterns were assessed in eight different behavioral situations in two lines of mice, BR and BS, previously selected for their sensitivity to an anxiogenic benzodiazepine (BZ) receptor inverse agonist, Methyl beta-carboline-3-carboxylate (beta-CCM). BR is highly resistant, and BS, highly sensitive to beta-CCM-induced seizures. Tests used included an assessment of general locomotor activity, several situations classically used for measuring fear-motivated behaviors (open field, thigmotaxis, elevated plus-maze, light-dark discrimination, staircase), a test for measuring exploration (holeboard), and a test for measuring nociception (hot-plate). In the absence of beta-CCM, the results provide evidence of reduced motor activity and higher levels of anxiety in the BR line as compared to the BS line.

Animals↗
PubMed1999

Radial maze learning in two inbred mouse strains and their reciprocal congenics for the non-pseudoautosomal region of the Y chromosome.

The effect of the non-pseudoautosomal region of the Y chromosome on spatial learning in a radial maze task was examined in two inbred mouse strains, NZB and CBA/H, and their respective congenics for the Y(NPAR). Seven variables reflecting learning performance, learning strategy and lateralisation were measured. We found no substantial effect of the Y(NPAR) on radial maze learning, but modest influences on behavioral strategies. These findings are in agreement with previous results regarding the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields.

Animals↗
PubMed1999

Mice selected for differences in sensitivity to a benzodiazepine receptor inverse agonist vary in intermale aggression.

Brain gamma-aminobutyric acid (GABA) levels are involved in intermale aggression in mice. It was therefore expected that animals genetically selected for their sensitivity to the convulsive effects of methyl beta-carboline-3-carboxylate (beta-CCM; BS, beta-CCM sensitive, and BR, beta-CCM resistant), a benzodiazepine (BZ) inverse agonist that specifically binds to the BZ site on the GABA-A receptor complex, would differ in their levels of aggressive behavior. Using two different aggression tests, in two independent experiments, we showed that BS mice are more aggressive than BR animals. The precise mechanisms underlying the observed line differences in beta-CCM sensitivity and aggression remain to be determined.

Aggression↗
PubMed1999

Further phenotypical characterisation of two substrains of C57BL/6J inbred mice differing by a spontaneous single-gene mutation.

Males from two substrains of C57BL/6J mice, which have been found to differ for open-field exploration, radial-maze learning, and the sizes of their hippocampal intra- and infra-pyramidal mossy fibre (IIPMF) terminal fields, were compared for offensive aggression, thermoregulatory nest-building, and their behaviour in the Light-Dark choice test. The substrain with the smaller IIPMF showed higher aggression and more nest-building behavior than the one with the larger IIPMF, whereas only tentative differences were found in the Light Dark choice test. These findings confirm and expand on previously found genetic links between the IIPMF and behaviours in mice. These substrains provide a powerful tool to localise the gene involved and subsequently investigate the pathway leading from gene to behaviour.

Animals↗
PubMed1998

Genetic selection of mouse lines differing in sensitivity to a benzodiazepine receptor inverse agonist.

Mice were selectively bred according to their sensitivity or their resistance to the convulsive effects of a 4-mg/kg dose of methyl beta-carboline-3-carboxylate (beta-CCM), a benzodiazepine (BZ) receptor inverse agonist. The selection proved to be easy, with a clear separation of the two lines, convulsing with short latencies or resistant, already at the first generation of selection. Selection of a third line of animals convulsing with long latencies did not succeed. 3H-Ro 15-1788 binding analysis provided evidence for a strong decrease in Bmax in the resistant line.

Animals↗
PubMed1998

A multivariate quantitative-genetic analysis of behavioral development in mice.

The present experiment attempted a behavior-genetic dissection of early behavioral development in laboratory mice. To this end, we used a full, replicated diallel cross to uncover the genetical architecture as well as the multivariate genetic structure underlying early behavioral ontogeny. A number of standard sensorimotor tests were administered on postnatal Days 3, 5, 8, 10, 13, 17, and 22 to a total of 622 pups from 120 litters (4-6 pups per litter) from a four times replicated complete diallel cross between five inbred mouse strains. The first day on which an animal showed adult performance was taken as its score on that test. MANOVA did not show any effects of the pup's sex on the speed of development. Hayman's analysis of variance for diallel tables indicated no or only weak additive-genetic effects. Dominance was absent in almost all cases, except for the auricular startle response, where weak directional dominance for fast development was found. These results are in accordance with an evolutionary past of directional selection for well-canalized development. Factor analyses of the phenotypic and additive-genetic correlation matrices indicate that at least two factors are necessary to describe the behavioral variation.

Adaptation, Psychological↗
PubMed1997

Hippocampal morphology and open-field behavior in Mus musculus domesticus and Mus spretus inbred mice.

Mus spretus is extensively used in interspecific mouse backcross analyses employed to generate genetic linkage maps. However, little is known about its behavior and neuroanatomy, phenotypes for which large interstrain differences have been observed in Mus musculus domesticus. Behavioral and hippocampal neuroanatomical variables were measured in adult male mice from the inbred strains C57BL/6J (Mus musculus domesticus) and SEG (Mus spretus). Clear differences were found for behavioral responses to novelty in an open field, SEG being much less active than C57BL/6J. Morphometrical analysis of hippocampal terminal fields, visualized with Timm's stain, revealed strain differences only for the size of the intra- and infrapyramidal mossy fiber terminal fields, which were about 3 x larger in C57BL/6J than in SEG. In addition, absolute left-right differences were larger in SEG for the stratum radiatum and stratum oriens. In spite of these behavioral and neuroanatomical differences, the phenotypical scores obtained for SEG do not exceed the range observed for Mus musculus domesticus inbred strains.

Animals↗
PubMed1996

Genetic variation in the morphology of the septo-hippocampal cholinergic and GABAergic systems in mice: II. Morpho-behavioral correlations.

We investigated the contribution of the septo-hippocampal cholinergic and GABAergic system to spatial and nonspatial aspects of learning and memory that had previously been found to correlate with the extent of the hippocampal intra- and infrapyramidal mossy fiber projection in different inbred mouse strains. The following cholinergic and GABAergic markers were measured in the septi and hippocampi of male mice: the number of cholinergic and parvalbumin-containing neurons in the medial septum/vertical limb of the diagonal band of Broca (MS/vDB), the number of septo-hippocampal cholinergic and GABAergic projection neurons, the density of cholinergic fibers in different hippocampal subfields, and the density of muscarinic receptors (predominantly M1 and M2) in the hippocampus. In addition, animals were behaviorally tested for spatially dependent and activity-dependent variables in a water maze and spatial and nonspatial working and reference memory in different experimental set-ups in an eight-arm radial maze. Using only those variables for which significant strain differences were obtained, we looked for covariations between behavior and neuroanatomy. The density of cholinergic fibers in the dentate gyrus was significantly correlated with activity-dependent learning in the water maze, whereas the number of septo-hippocampal cholinergic projection neurons correlated with spatial and, to a lesser extent, also with nonspatial aspects of radial maze learning. Only weak correlations were found between receptor densities and behavioral traits. From these data we conclude that variations in the septo-hippocampal cholinergic system, like variations in the mossy fiber projection, entail functional consequences for different types of maze learning in mice.

Acetylcholinesterase↗
PubMed1996

Paw preference and intra-/infrapyramidal mossy fibers in the hippocampus of the mouse.

The size of the intra-/infrapyramidal mossy fiber projections (IIP-MF) and their left/right asymmetry were assessed in 86 mice of either sex, including 26 animals from two mouse lines bred for strong or weak paw preference, 38 mice of a randomly bred F3 generation derived from an eight-way cross, and 22 mice with variably sized corpora callosa in which only the left hippocampus was measured. Prior to morphometry, all mice were tested for paw preference. In addition, we compared the strain means in paw preference as observed in nine inbred mouse strains with known differences in their IIP-MF distribution. Mice bred for strong paw preference had a 70% larger IIP-MF projection than weakly lateralized and dyscallosal mice; random-bred mice fell in-between the extremes. The individual scores of the strength of paw preference were positively correlated with the extent of the IIP-MF. Among the inbred strains, the extent of the IIP-MF was similarly correlated with the strength of paw preference. The acallosal mice showed a significant negative correlation between extent of the IIP-MF projection and test-retest reliability of paw use. The left-right asymmetry of the IIP-MF was significantly and positively correlated with the direction of paw preference in the entire sample. We conclude that size and asymmetry of the IIP-MF projection are some of the many factors influencing the direction of paw preference and its strength, albeit moderately. We hypothesize that mice with larger IIP-MF projections use a given paw more consistently, being perhaps more resistant to interferences, and that left-right asymmetries of the IIP-MF may bias and/or reinforce an initial choice of a paw. In addition, the data provide another example of correlations between IIP-MF variations and nonspatial behavior.

Animals↗
PubMed1996

Hippocampal morphology in the inbred mouse strains NZB and CBA/H and their reciprocal congenics for the nonpseudoautosomal region of the Y chromosome.

The effects of the nonpseudoautosomal region of the Y chromosome (YNPAR) on hippocampal morphology have been investigated in the inbred mouse strains NZB/BINJ and CBA/H, using comparisons between the two parentals and their respective congenics N.H-YNPAR and H.N-YNPAR. Results obtained depend upon the hippocampal variable measured. YNPAR had no effect on the sizes of the stratum oriens, hilus, or mossy fiber terminal fields (both suprapyramidal and intra- and infrapyramidal). However, in interaction with the strain background, it affected the strata lacunosum-moleculare, radiatum, and pyramidale. Possible relationships among gene(s), mossy fiber terminal fields, and intermale aggression are discussed.

Aggression↗
PubMed1996

Prenatal effects of parity on behavioral ontogeny in mice.

In mice, parity and previous experience with pups may influence a mother's behavior towards her pups, thus possibly causing postnatal maternal effects on the subsequent development of the pups. The present experiment addressed the question whether parity also might have prenatal effects. We studied 622 pups from second or third litters that originated from 25 genetically different populations and had been fostered to random-bred lactating females. Development of responses was significantly delayed in mice from third litters, when compared to pups from second litters in three out of five sensorial and four out of eight motor tests. In addition, pups from second litters initially were slightly heavier than those from third litters. This difference in body weight disappeared after the 10th day postnatally. However, it should be noted that effect sizes were quite small.

Aging↗