Biomedical subjects

H Schwegler

Publications and source records attributed to H Schwegler.

At least 19 recordsLinked to original sources

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↗

PubMed1994

Cholinergic and GABAergic septo-hippocampal projection neurons in mice: a retrograde tracing study combined with double immunocytochemistry for choline acetyltransferase and parvalbumin.

The present experiments were directed to determine the proportions of the cholinergic and GABAergic septo-hippocampal projection neurons in NMRI mice. For the labeling of the septal neurons we used a double immunocytochemical method combined with retrograde transport of wheatgerm agglutinin apo-horseradish peroxidase-gold (WAHG) injected unilaterally into the hippocampus. Monoclonal antibodies against choline acetyltransferase (ChAT) and parvalbumin (PARV) were used as markers for cholinergic and GABAergic neurons in the medial septum/diagonal band complex (MS/DB). Both antibodies were visualized in the same section using the ABC detection system with diaminobenzidine and 4-chloro-1-naphtol as chromogens. Cholinergic and PARV-containing neurons are coexisting in the MS/DB. About 38% of all retrogradely labeled neurons were ChAT-positive whereas only 10% of all retrogradely labeled cells were immunostained for PARV. On the other hand, 40% of all ChAT-positive neurons and about 24% of all PARV-positive neurons were retrogradely labeled. No double immunolabeled neurons were detected. The proportion of GABAergic neurons may have been underestimated because immunostaining for PARV only labels a subpopulation of GABAergic neurons. The present results were compared with those of previous studies in rats. They may serve as a basis of further comparative studies in mice.

Animals↗

PubMed1994

Fluctuations in circulating cell numbers following chemotherapy or bone marrow transplant.

We study the effect of noise on the behaviour of a dynamic cell population model in which cell replication and maturation take place simultaneously. We assume that the maximum proliferative potential v fluctuates uniformly about a mean value of v, and show that a decrease in v and/or the input flux uin into the population can lead to an increase in the variance in the cellular efflux uf. We draw a qualitative correspondence between this behaviour and the commonly observed increase in the variance of circulating blood cell numbers following chemotherapy and radiotherapy, both of which lead to a decrease in v and uin, and bone marrow transplant which probably corresponds to a decrease in uin.

Blood Cells↗

PubMed1992

Hippocampal mossy fiber distribution does not correlate with two-way active avoidance performance in backcross lines derived from inbred mouse strains DBA/2 and C3H.

To elucidate the relation of genetically induced variations in two-way active avoidance performance and the extent of the hippocampal infra/intrapyramidal mossy fiber system (IIP-Mf) in inbred mouse strains DBA/2 (high performance, small IIP-Mf) and C3H (low performance, large IIP-Mf) we investigated a backcross line containing the DBA/2-derived genetic determinants for high avoidance performance in a C3H background. In the seventh backcross generation variations in performance analogous to the original strains were observed whereas the extent of mossy fibers was nearly homogeneous. This result suggests that both variables are determined by separate genetic factors at least in these strains and that differences in mossy fiber distribution are not an essential prerequisite for different active avoidance performance.

Afferent Pathways↗

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

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

Proliferation and differentiation of glial fibrillary acidic protein-immunoreactive glial cells in organotypic slice cultures of rat hippocampus.

The present paper deals with the proliferation and differentiation of glial cells in organotypic slice cultures of the rat hippocampal formation. Transverse slices of hippocampus of newborn to five-day-old rats were cultivated using the roller tube technique. To study the development of glial cells under these conditions, the slice cultures were processed for immunostaining employing antibodies against the glial fibrillary acidic protein. The proliferation of glial cells was studied in double-labeling experiments employing glial fibrillary acidic protein-immunostaining and the bromodeoxyuridine technique. The three-dimensional glial scaffold in the cultures was analysed in semithin and ultrathin cross-sections through the slice cultures after varying periods following explanation. Our results can be summarized as follows: 1. At all intervals after explanation of the slices there are numerous glial fibrillary acidic protein-positive cells with morphological characteristics of astrocytes. 2. With some modifications, the differentiation of astrocytes and their processes follows similar rules as observed in the hippocampus in vivo. A radial glial scaffold is also formed in the cultures. However, in cultures, a regular pattern of radial fibers is more obvious in the hippocampus proper than in the dentate gyrus. This glial scaffold persists after 20 days in vitro whereas it is known to disappear after the first postnatal week in vivo. 3. Bromodeoxyuridine-positive nuclei of glial cells were found at all time periods after explanation. After short incubation periods, they were most frequent in the "ventricular" zones of the cultures. Following longer incubation periods after bromodeoxyuridine administration, proliferating cells were found throughout the cultures, covering and underlying the cultured tissue. A rim of laterally migrating astrocytes completely surrounds the cultures. Our results demonstrate that glial cells proliferate and differentiate under the present culture conditions. After three weeks of incubation the whole slice culture is surrounded by a glial cover which may play an important role for the survival and differentiation of the cultured hippocampal neurons.

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

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↗

PubMed1990

Plasticity of identified neurons in slice cultures of hippocampus: a combined Golgi/electron microscopic and immunocytochemical study.

The combined Golgi/electron microscope (EM) technique and immunocytochemistry for glutamate decarboxylase (GAD) were used to study the differentiation of pyramidal neurons and GABAergic inhibitory non-pyramidal cells in slice cultures of rat and mouse hippocampus. Golgi-impregnated and gold-toned cultures showed the characteristic curved structure of the Ammon's horn. Hippocampal regions CA1, CA3 and fascia dentata could easily be recognized. Pyramidal neurons in CA1 displayed all characteristics of this cell type known from Golgi studies in situ. A triangular cell body gives rise to a main apical dendritic shaft which gives off several side branches. Basal dendrites and the axon originate at the basal pole of the cell body. Apical and basal dendrites are densely covered with spines. As a characteristic feature of the cultured pyramidal cells, numerous spines were observed on the cell body. Most likely due to flattening of the slice during incubation, the pyramidal neurons in CA1 are no longer arranged in a densely packed layer. This results in more space between cell bodies which is filled in by numerous horizontal and basal dendrites originating from the pyramidal cell perikaryon. CA1 pyramidal neurons in slice cultures of the rat or mouse thus resemble the pyramidal neurons in the CA1 region of the primate hippocampus where a similar loose distribution of cell bodies is found. In the electron microscope, cell bodies and dendritic shafts of the gold-toned pyramidal cells formed symmetric synaptic contacts with presynaptic terminals. Numerous boutons were observed that established asymmetric synaptic contacts on gold-toned spines of peripheral pyramidal cell dendrites. This suggests that considerable synaptic reorganization takes place because in situ spines on peripheral dendritic segments are contacted mainly by extrinsic afferents. Like in situ, at least some of the terminals that establish symmetric synaptic contacts are GABAergic. In our immunocytochemical study we observed numerous GAD-positive terminals that formed a dense pericellular plexus around immunonegative cell bodies of pyramidal neurons. In the electron microscope these structures were identified as presynaptic boutons which formed symmetric synaptic contacts on cell bodies and dendritic shafts. They most likely originated from the GAD-positive neurons scattered in all layers of the slice culture. Our results have shown that the main cell types in the hippocampus, pyramidal neurons and GABAergic inhibitory non-pyramidal cells, survive and differentiate under the present culture conditions.(ABSTRACT TRUNCATED AT 400 WORDS)

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

Hippocampal mossy fiber distribution and long-term potentiation in two inbred mouse strains.

We studied long-term potentiation in the inbred mouse strains DBA/2 and C3H/He known to be different in both hippocampal mossy fiber distribution and several aspects of learning. Tetanic stimulation of mossy fibers resulted in a significantly stronger increase of the population spike amplitude in the CA3 pyramidal cell layer of C3H mice. This result suggests that the extent of the CA3 hippocampal mossy fiber projection correlates with synaptic efficacy in mice.

Action Potentials↗

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

Genetic selection for novelty-induced rearing behavior in mice produces changes in hippocampal mossy fiber distributions.

Previous investigations in mice revealed the existence of a set of genes that influence variations in hippocampal anatomy as well as variations in behavioral responses to novelty. In particular, a positive genetic correlation was found between the size of the intra- and infrapyramidal mossy fiber (iip-MF) projection and rearing frequency in an open-field. On the basis of these findings, we hypothesized that genetic selection for rearing would entail correlated changes in hippocampal morphology. This was tested in the inbred selection lines SRH (selection for rearing: high) and SRL (selection for rearing: low). As expected, the SRH mice appeared to possess iip-MF terminal fields that were larger than those of the SRL mice. Because the behavioral difference between the two lines is most probably caused by a single genetic unit, these animals represent valuable material for molecular-genetic investigations into the mechanisms that control behavioral and neuroanatomical variation.

Animals↗