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J H van Abeelen

Publications and source records attributed to J H van Abeelen.

At least 19 recordsLinked to original sources

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.

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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.

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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.

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Genetic control of hippocampal cholinergic and dynorphinergic mechanisms regulating novelty-induced exploratory behavior in house mice.

Neurobehavioral genetics endeavors to trace the pathways from genetic and environmental determinants to neuroanatomical and neurophysiological systems and, thence, to behavior. Exploiting genetic variation as a tool, the behavioral sequelae of manipulating these neuronal systems by drugs and antisera are analyzed. Apart from research in rats, this paper deals mainly with the genetically-influenced regulation in mice of exploratory behaviors that are adaptive in novel surroundings and are hippocampally-mediated. Special attention is paid to neuropeptidergic, GABAergic, and cholinergic synaptic functions in the mouse hippocampus. The behaviorally different inbred mouse strains C57BL/6 and DBA/2 show opposite reactions (reductions and increases, respectively, in exploration rates) to peripheral and intrahippocampal injections with agents that interfere with peptidergic, cholinergic, and GABAergic neurotransmission. These findings can be explained by an interdependent over-release of opioids, arrested GABA release, and excess acetylcholine in the hippocampal neuronal network of DBA/2 mice, as compared to C57BL/6 mice where these systems are functionally well balanced. Very similar results have been obtained with the lines SRH and SRL, derived from C57BL/6 and DBA/2, and genetically selected for rearing behavior. Most probably, the opioids act to disinhibit exploratory responses. An additional genetic approach is mentioned, in which four inbred mouse strains and one derived heterogeneous stock are used for estimating genetic correlations between structural properties of the hippocampal mossy fibers and levels of hippocampal dynorphin B, on the one hand, and frequencies of exploratory responses to environmental novelty, on the other.

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Distribution of dynorphin B and methionine-enkephalin in the mouse hippocampus: influence of genotype.

Immunohistochemical techniques were used to localize dynorphin B and methionine-enkephalin in the mouse hippocampus. Methionine-enkephalin-like immunoreactivity was found within the somata of interneurons distributed mainly in and around the CA1 stratum pyramidale and stratum granulosum as well as in the mossy fibers. Dynorphin B appeared to be confined to the mossy fiber pathway. In addition, we observed a difference between the inbred mouse strains DBA/2 and C57BL/6 with regard to the areas of the dynorphinergic mossy fiber projections: the intra- and infrapyramidal terminal fields were larger in the latter group.

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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.

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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.

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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.

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A method permitting precise trimming of resin-embedded tissue for ultrathin sectioning in pre-embedding immunoelectronmicroscopy.

Due to the high complexity of the mammalian central nervous system, sampling of immunohistochemically processed brain tissues for electronmicroscopy requires an accurate and reliable technique. For this reason, the flat-embedding method, which allows light microscopical examination of tissue before sampling, is generally employed. Because of the osmification process, however, the tissue is blackish and opaque which hampers light microscopical selection of tissue areas of interest. We have found that tissue translucency is highly improved by an osmification process using an osmium tetroxide-ferrocyanide mixture. We describe a transilluminated chuck that enables visualization of immunostaining in specimens mounted on a trimming instrument, thus allowing for extremely precise sampling of the tissue.

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Zinc-induced peripheral anosmia and behavioral responses to novelty in mice: a quantitative-genetic analysis.

Adult male mice were made anosmic by intranasal flushing with a 5% zinc sulfate solution. Twelve behavioral variables were measured in treated as well as saline-irrigated control animals placed in a novel environment. The genetic underpinnings and the genotype-treatment interactions with regard to these behaviors were analyzed in a classical Mendelian cross between the inbred strains C57BL/6 and DBA/2 and in a full 4 X 4 diallel cross, replicated five times, between these strains and strains C3H/St an CPB-K. Based on the hypothesis of an evolutionary history of directional selection for a well-balanced information-processing system, one might expect directional dominance for decrease in exploration after anosmization. Although decreases were found for several behavioral phenotypes, only few and relatively unimportant genotype-treatment interactions were present. This absence of any kind of genetic variation for behavioral change after anosmization points to an extremely strong directional selection which has eliminated all less favorable alleles. The findings support the hypothesis of directional selection for an efficient olfactory information-processing system.

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The genetic architecture of behavioural responses to novelty in mice.

The genetic architectures of 12 behavioural variables measured in adult male mice placed in a novel environment were analysed in a replicated 4 X 4 diallel cross. The results were combined with those obtained in a classical cross involving two of the four strains. Based on the hypothesis of an evolutionary history of stabilising selection for mouse exploratory behaviour, we expected additive genetic effects and ambidirectional dominance. Such genetic architectures were actually found for those exploratory behaviours where epistatic effects were of minor importance. Similar findings emerged for some non-exploratory phenotypes. All behaviours analysed appeared to be polygenically controlled.

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Role of hippocampal Met-enkephalin in the genotype-dependent regulation of exploratory behavior in mice.

Intrahippocampal microinjections with anti-Met-enkephalin antiserum enhanced novelty-induced vertically oriented exploratory acts and horizontal locomotor activity in inbred mouse strain DBA/2 and reduced these behaviors in C57BL/6 so that strain differences originally present between the normal serum controls were eliminated after antiserum treatment. These opposite effects suggest that hippocampal Met-enkephalin participates in the genotype-dependent control of mouse exploration.

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A genetically controlled hippocampal transmitter system regulating exploratory behavior in mice.

Male C57BL/6 and DBA/2 mice were intrahippocampally microinjected with muscimol (0.5 microgram), given 15 min prior to individual 20-min exploration tests in a novel environment, and compared to saline controls. The GABA agonist reduced various exploratory acts and locomotor activity in strain C57BL/6 and increased the scores in DBA/2. In conjunction with similar opposite effects previously found with intra-hippocampal methylscopolamine and naloxone, these findings suggest that the opioid modulation of the hippocampal cholinergic mechanism which facilitates behavioral responses to novelty in mice is effectuated indirectly through an inhibitory GABAergic system. The functioning of these regulatory systems appears to depend on genotype.

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Effects of intrahippocampally-injected naloxone and morphine upon behavioural responses to novelty in mice from two selectively-bred lines.

To examine the peptidergic regulation of behavioural responses to novelty, 5-month-old male mice from the inbred selection lines SRH (selected for rearing frequency: high) and SRL (selected for rearing frequency: low) were intrahippocampally micro-injected (0.5 microliter) with either the opiate antagonist naloxone (0.3 microgram), or the opiate agonist morphine (1.0 microgram), or saline vehicle alone, given 15 min prior to individual exposure to 20-min exploration tests in a novel environment. Naloxone exerted opposite effects upon various exploratory acts and locomotor activity in the two strains, that is, it decreased the scores in SRH and augmented them in SRL, while morphine depressed the scores in both. It is suggested that an excess of opioids in SRL, as compared to SRH, is attenuated by this dose of naloxone. In addition to previously obtained evidence of a genotype-dependent cholinergic mechanism in the mouse dorsal hippocampus controlling exploratory responses to novelty, these findings indicate that hippocampal opioid peptides are also involved in the genotype-dependent regulation of exploration.

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Behavioural responses to novelty in two inbred mouse strains after intrahippocampal naloxone and morphine.

Male C57BL/6 and DBA/2 mice were injected intrahippocampally with either naloxone (0.5 microgram) or morphine (1.0 microgram), or saline vehicle alone and, after 15 min, some 12 behavioural components carried out in a novel environment were recorded for 20 min. Naloxone reduced exploratory rearing responses, wall-leaning and object-sniffing in strain C57BL/6 and augmented these behaviours in strain DBA/2, while morphine depressed the scores in both. In conjunction with previously obtained evidence that the mouse hippocampus contains a genotype-dependent cholinergic mechanism which regulates responses to novelty, these findings support the hypothesis that hippocampal opioid peptides modulate the cholinergic control of exploration in mice, possibly indirectly through GABAergic pathways. In contrast, locomotor activity, defaecation and tail elevation remained practically unaffected by the two drugs, and grooming showed another kind of genotype-treatment interaction, that is to say, after morphine.

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