Biomedical subjects

R Gerlai

Publications and source records attributed to R Gerlai.

49 records · Page 3Linked to original sources

PubMed1996

Impaired motor learning performance in cerebellar En-2 mutant mice.

Mice homozygous for a null mutation in their En-2 gene exhibit cerebellar neuroanatomical alterations including absence and misplacements of specific fissures and size reduction. The present study investigated cerebellar function by comparing the behavior of age-matched homozygous and heterozygous En-2 mutant and wild-type mice. Motor function of the mutants was found normal in several situations. Habituation to novelty in the open field was not significantly different in mutants. However, in a motor learning paradigm, the rotating rod, the performance of homozygous mutant mice improved significantly less than that of the heterozygous mice which were also significantly impaired compared to wild-type mice. Unlike other cerebellar mutants in which severe motor or sensory defects are obvious, the En-2 mouse model offers a unique tool to study the role of cerebellum in complex behavioral phenomena, including motor learning, without confounding effects.

Animals↗

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

Abnormal exploratory behavior in transgenic mice carrying multiple copies of the human gene for S100 beta.

S100 beta, a calcium-binding brain protein, has been implicated in brain development and hippocampal neurophysiology including long-term potentiation. Its gene maps to chromosome 21, which is duplicated in Down syndrome. S100 beta levels are elevated in both Down syndrome and Alzheimer's disease, human neurodegenerative diseases associated with mental retardation and dementia. To investigate whether or not elevated S100 beta levels can cause brain dysfunctioning in mammals, transgenic mice carrying multiple copies of the human S100 beta gene were generated. Several independent lines of transgenic mice were compared to age-matched normal control mice of identical genetic background (CD1) by measuring their exploratory behaviors in novel situations. Transgenic mice exhibited a range of defects including female specific hyperactivity, lack of habituation to novelty and reduced T-maze spontaneous alternation rate. Although the neuroanatomical or physiological substrate of these abnormalities is unknown, they are similar to the behavioral manifestations of hippocampal dysfunction. The S100 beta mouse offers one of the first opportunities to investigate the relationship between over-expression of a human chromosome 21 gene product and abnormal behavior and brain functioning.

Animals↗

PubMed1994

Myelination in the absence of myelin-associated glycoprotein.

The hypothesis that myelin-associated glycoprotein (MAG) initiates myelin formation is based in part on observations that MAG has an adhesive role in interactions between oligodendrocytes and neurons. Furthermore, the over- or underexpression of MAG in transfected Schwann cells in vitro leads to accelerated myelination or hypomyelination, respectively. Here we test this idea by creating a null mutation in the mag locus and deriving mice that are totally deficient in MAG expression at the RNA and protein level. In adult mutant animals the degree of myelination and its compaction are normal, whereas the organization of the periaxonal region is partially impaired. Mutant animals show a subtle intention tremor. Our findings do not support the widely held view that MAG is critical for myelin formation but rather indicate that MAG is necessary for maintenance of the cytoplasmic collar and periaxonal space of myelinated fibres.

Animals↗

PubMed1994

T-maze spontaneous alternation rate is decreased in S100 beta transgenic mice.

S100 beta, a calcium-binding brain specific protein, may affect both brain development and hippocampal long-term potentiation. S100 beta levels are elevated in Down syndrome (DS), and the gene for S100 beta is located on chromosome 21, which is duplicated in DS. To test the hypothesis that, elevated levels of S100 beta cause behavioral alterations in a mammalian system, 3 transgenic mouse lines with multiple copies of the human gene for S100 beta were derived and behaviorally tested. The spontaneous alteration behavior of transgenic and normal littermate mice were compared in a T maze during a 15-trial test. The overall alteration rate was found to be significantly decreased in the transgenic mice compared with their normal littermates. The S100 beta transgenic mouse model offers one of the first opportunities to investigate the relation between overexpression of a human chromosome 21 gene product and abnormal behavior and brain function.

Animals↗

PubMed1993

Female specific hyperactivity in S100 beta transgenic mice does not habituate in open-field.

S100 beta, a calcium-binding brain specific protein, may affect brain development and long-term potentiation. Its gene maps to a region of chromosome 21 duplicated in Down's Syndrome (DS), and its levels are elevated in DS. To test the hypothesis that elevated S100 beta levels cause brain dysfunction in a mammalian system, transgenic mice carrying multiple copies of the human S100 beta gene have been generated and their locomotory patterns are analyzed in open field situations. Female-specific hyperactivity was observed in 2-month-old and in 12-month-old transgenic mice, which rules out the previous speculation that postmenopausal hormonal changes constitute a necessary factor in this behavioral abnormality. Analysis of temporal patterns of activity showed a profound abnormality in transgenic females: the initially elevated activity quickly habituated in males and in normal females, however, its level remained high in the transgenic females throughout the 9-min recording session. These observations are compatible with the suggestion that hippocampal function is abnormal in the females of S100 beta transgenic mice.

Animals↗

PubMed1993

Female transgenic mice carrying multiple copies of the human gene for S100 beta are hyperactive.

Down syndrome (DS) (trisomy 21) is the most frequent genetic cause of mental retardation in man. The gene coding for the beta subunit of human S100 protein (S100 beta) has been mapped to chromosome 21. The dimeric form of S100 beta may function as a neurotrophic factor in the CNS and may also influence the establishment of hippocampal long-term potentiation (LTP). To study the behavioral consequences of overexpression of S100 beta in an animal model, we derived four lines of transgenic mice carrying multiple copies of the human S100 beta gene. The human S100 beta gene was expressed in the brain of these mice in a cell-specific and gene-dose-dependent manner. The motor and posture patterns of 16-month-old transgenic mice and their control (non-transgenic) littermates were studied in two tests, open field and bar-crossing, in order to examine novelty induced exploratory activities. Transgenic female mice were significantly hyperactive in both tests in comparison with their female control littermates. These differences were independent of the line of origin of the mice suggesting a causal relationship between the observed hyperactivity and the presence of multiple copies of the integrated human S100 beta gene. In contrast, transgenic males were not hyperactive in comparison with controls. Neither male nor female transgenic mice displayed any coordination defects. We speculate about how an interaction between the effects of elevated S100 beta levels and female specific hormonal changes could have resulted in the observed female restricted hyperactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Learning to find the opponent: an ethological analysis of the behavior of paradise fish (Macropodus opercularis) in intra- and interspecific encounters.

In Experiment 1, 15 behavior patterns of male paradise fish (Macropodus opercularis; n = 72) toward a male conspecific, a male of another species, or no stimulus were recorded, both in home and novel situations. In Experiment 2, the same behaviors were recorded in a runway, and the same stimuli were used as reinforcers in the goal box (n = 18). A typical learning curve was seen when the subject found a male paradise fish in the goal box, learning was followed by apparent extinction when another species was found in the goal box, and few signs of learning were seen when the goal box was empty. Performance of the fish in both experiments can be accounted for by a strong aggressive motivation, a less strong but clear general curiosity, and habituation to the experimental procedure. In contrast to recent assertions in the literature, we conclude that aggressive behavior clearly can serve as a reinforcer in an instrumental learning situation.

Aggression↗

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

Genotype-environment interaction and the correlation structure of behavioral elements in paradise fish (Macropodus opercularis).

Three inbred strains and all their possible F1 crosses were monitored in one familiar and three unfamiliar situations. Their behavior was described by species-specific elements of the ethogram. Genetic variability was demonstrated both for behavioral elements and for factors extracted by Principal Components Analyses (PCA). We studied how the behavior of genetically different fish changed across situations and examined the interrelations both among variables measured in one situation and between those measured in different ones. Behavioral changes across situations proved to be different for certain strains and crosses, that is, genotype-environment interaction was found. The PCA's carried out for the 4 situations separately yielded unlike factor structures. Another PCA, in which all the variables were included, proved that there was correlation among certain variables measured in different situations. In general, it seems that the corresponding behavioral elements do not always represent the same phene in different situations. We discuss how the genotype-environment interactions can be interpreted, try to define behavioral strategies using the extracted factor structures, and construct a model for the organization of Macropodus behavior.

Animals↗

PubMed1989

Diallel genetic analysis of the elements of paradise fish's (Macropodus opercularis L.) behavior in familiar and novel situations.

Elements of the paradise fish's ethogram were recorded in 1 familiar and 3 different unfamiliar situations and the inheritance of these behavioral elements was investigated employing a five times replicated diallel cross between 3 inbred strains. A generalized Hayman Analysis of Variance and a Variance Covariance Analysis were performed to estimate genetic effects and parameters, such as, additive genetic variance, different sorts of dominance variance, reciprocal effects, direction and degree of dominance, ratio between the frequency of dominant and of recessive alleles, minimum number of effective factors and heritabilities, etc. Knowing the genetic architecture, we make inferences about the possible evolutionary past of the behavioral elements and explain why selection might favor certain types of paradise fish's behavior in particular circumstances. In several cases a possibility of "monogenic" inheritance emerged. We explain this finding and conclude that in a cross experiment where the inheritance of phenotypical units are investigated by employing only a few genetically different strains this result may be expected.

Alleles↗

PubMed1987

The behaviour of the paradise fish (Macropodus opercularis) in two different open-fields. A correlation study.

The behaviour of the paradise fish in a traditional "closed" and in a new "transparent" open-field was investigated. The traditional way of measuring ambulation scores was extended by recording ethologically defined behaviour units. The correlations found between the scores measured in the "closed" field and those measured in the "transparent" field are discussed in this paper.

Animals↗

PubMedDate not supplied

Overexpression of a calcium-binding protein, S100 beta, in astrocytes alters synaptic plasticity and impairs spatial learning in transgenic mice.

Recent evidence suggests that slowly propagating Ca2+ waves from astrocytes can modulate the function of neurons. Altering astrocytic calcium processes in vivo may therefore affect neuronal and behavioral phenotypes. Previously, we generated transgenic mice that overexpress an astrocytic calcium-binding protein, S100 beta. Immunocytochemistry and in situ hybridization showed elevated expression in the astrocytes of the hippocampus and other brain regions. Neurons in the hippocampus were negative for S100 beta. In this paper we analyze the hippocampal electrophysiology and learning properties of mice from two transgenic lines. Significant differences were found between the hippocampal slices of normal and transgenic mice in their response to high frequency (100 Hz) stimulation. The overall distribution of post-tetanic excitatory postsynaptic potentials (EPSP) of the slices from the transgenic mice was shifted significantly toward smaller values to a degree that 25% of slices exhibited depression. The altered hippocampal neurophysiology was accompanied by an impairment in a hippocampal-dependent learning task. Transgenic mice showed significant impairment in a spatial version of the Morris water maze, however, they performed normally in non-spatial tasks. Probe trials showed that transgenic mice, though significantly impaired, also acquired spatial information. The results suggested that the impairment was not due to motor dysfunction, impaired vision or motivation of the transgenic mice, findings compatible with a possible hippocampal mechanism. We conclude that overexpression of S100 beta in astrocytes impairs, but does not abolish, the ability to solve a spatial task, and it leads to a significantly decreased post-tetanic potentiation in the hippocampal slice. We hypothesize that the changes are due to calcium mediated processes. Our results support the notion that astrocytes are involved in higher brain functions.

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