Publications (7)24.83 Total impact
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Article: Hippocampal serotonin-1A receptor function in a mouse model of anxiety induced by long term voluntary wheel running.
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ABSTRACT: We have recently demonstrated that in C57/Bl6 mice long term voluntary wheel running is anxiogenic, and focal hippocampal irradiation prevents the increase in anxiety-like behaviors as well as neurobiological changes in the hippocampus induced by wheel running. Evidence supports a role of hippocampal 5-HT1A receptors in anxiety. Therefore, we investigated hippocampal binding and function of 5-HT1A receptors in this mouse model of anxiety. Four weeks of voluntary wheel running resulted in hippocampal subregion-specific changes in 5-HT1A receptor binding sites and function, as measured by autoradiography of [(3) H]8-OH-DPAT binding and agonist-stimulated binding of [(35) S]GTPγS to G proteins, respectively. In the dorsal CA1 region, 5-HT1A receptor binding and function were not altered by wheel running or irradiation. In the dorsal dentate gyrus and CA2/3 region, 5-HT1A receptor function was decreased by running, but also by irradiation. In the ventral pyramidal layer, wheel running resulted in a decrease of 5-HT1A receptor function, which was prevented by irradiation. Neither irradiation nor wheel running affected 5-HT1A receptors in medial prefrontal cortex, or in the dorsal or median raphe nuclei. Our data indicate that down-regulation of 5-HT1A receptor function in ventral pyramidal layer may play a role in anxiety-like behavior induced by wheel running. Synapse, 2013. © 2013 Wiley Periodicals, Inc.Synapse 03/2013; · 2.94 Impact Factor -
Article: Are you real? Visual simulation of social housing by mirror image stimulation in single housed mice.
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ABSTRACT: Individual housing of social species is a common phenomenon in laboratory animal facilities. Single housing, however, is known to inflict social deprivation with a number of detrimental consequences. Aiming to improve housing conditions of single housed rodents, we investigated the simulation of social housing by mirrors in a series of behavioural experiments and biochemical parameters in mice. We found that chronic mirror-image stimulation increased exploratory behaviours in the holeboard and novel cage tests, but did not alter anxiety, locomotor, or depression-like behaviours. Moreover, no influence on visual recognition memory was observed. Hippocampal brain-derived neurotrophic factor (BDNF) levels, a biomarker for enrichment effects, were unaltered. In line, mirror-image stimulation did not alter home cage behaviour in mice housed with and without mirrors when left undisturbed. Thus, though we found subtle behavioural effects after long-term mirror exposure, we conclude that the simulation of social housing by mirrors is not sufficient to gain the presumably beneficial outcomes induced by social housing.Keywords: Mice; Environmental enrichment; Mirrors; Single housing; Exploration.Behavioural brain research 01/2013; · 3.22 Impact Factor -
Article: The puzzle box as a simple and efficient behavioral test for exploring impairments of general cognition and executive functions in mouse models of schizophrenia.
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ABSTRACT: Deficits in executive functions are key features of schizophrenia. Rodent behavioral paradigms used so far to find animal correlates of such deficits require extensive effort and time. The puzzle box is a problem-solving test in which mice are required to complete escape tasks of increasing difficulty within a limited amount of time. Previous data have indicated that it is a quick but highly reliable test of higher-order cognitive functioning. We evaluated the use of the puzzle box to explore executive functioning in five different mouse models of schizophrenia: mice with prefrontal cortex and hippocampus lesions, mice treated sub-chronically with the NMDA-receptor antagonist MK-801, mice constitutively lacking the GluA1 subunit of AMPA-receptors, and mice over-expressing dopamine D2 receptors in the striatum. All mice displayed altered executive functions in the puzzle box, although the nature and extent of the deficits varied between the different models. Deficits were strongest in hippocampus-lesioned and GluA1 knockout mice, while more subtle deficits but specific to problem solving were found in the medial prefrontal-lesioned mice, MK-801-treated mice, and in mice with striatal overexpression of D2 receptors. Data from this study demonstrate the utility of the puzzle box as an effective screening tool for executive functions in general and for schizophrenia mouse models in particular.Experimental Neurology 01/2011; 227(1):42-52. · 4.70 Impact Factor -
Article: Endocannabinoids and voluntary activity in mice: runner's high and long-term consequences in emotional behaviors.
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ABSTRACT: The endocannabinoid system participates in the regulation of physical activity, although its role is not yet fully understood. Here, we highlight the impact of endocannabinoid signalling on voluntary wheel running in mice and discuss potential mechanisms involved such as hippocampal neurogenesis. Running-induced short-term and long-term alterations of emotional behaviors are scrutinized with regard to the question how endocannabinoids might be involved. While endocannabinoids seem to contribute to the motivational aspects of voluntary running in rodents, influencing the total distance covered most likely via CB1 receptors, they are less involved in the long-term changes of emotional behavior induced by voluntary exercise.Experimental Neurology 03/2010; 224(1):103-5. · 4.70 Impact Factor -
Article: Deletion of running-induced hippocampal neurogenesis by irradiation prevents development of an anxious phenotype in mice.
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ABSTRACT: Recent evidence postulates a role of hippocampal neurogenesis in anxiety behavior. Here we report that elevated levels of neurogenesis elicit increased anxiety in rodents. Mice performing voluntary wheel running displayed both highly elevated levels of neurogenesis and increased anxiety in three different anxiety-like paradigms: the open field, elevated O-maze, and dark-light box. Reducing neurogenesis by focalized irradiation of the hippocampus abolished this exercise-induced increase of anxiety, suggesting a direct implication of hippocampal neurogenesis in this phenotype. On the other hand, irradiated mice explored less frequently the lit compartment of the dark-light box test irrespective of wheel running, suggesting that irradiation per se induced anxiety as well. Thus, our data suggest that intermediate levels of neurogenesis are related to the lowest levels of anxiety. Moreover, using c-Fos immunocytochemistry as cellular activity marker, we observed significantly different induction patterns between runners and sedentary controls when exposed to a strong anxiogenic stimulus. Again, this effect was altered by irradiation. In contrast, the well-known induction of brain-derived neurotrophic factor (BDNF) by voluntary exercise was not disrupted by focal irradiation, indicating that hippocampal BDNF levels were not correlated with anxiety under our experimental conditions. In summary, our data demonstrate to our knowledge for the first time that increased neurogenesis has a causative implication in the induction of anxiety.PLoS ONE 01/2010; 5(9). · 4.09 Impact Factor -
Article: Voluntary exercise induces anxiety-like behavior in adult C57BL/6J mice correlating with hippocampal neurogenesis.
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ABSTRACT: Several studies investigated the effect of physical exercise on emotional behaviors in rodents; resulting findings however remain controversial. Despite the accepted notion that voluntary exercise alters behavior in the same manners as antidepressant drugs, several studies reported opposite or no effects at all. In an attempt to evaluate the effect of physical exercise on emotional behaviors and brain plasticity, we individually housed C57BL/6J male mice in cages equipped with a running wheel. Three weeks after continuous voluntary running we assessed their anxiety- and depression-like behaviors. Tests included openfield, dark-light-box, elevated O-maze, learned helplessness, and forced swim test. We measured corticosterone metabolite levels in feces collected over a 24-h period and brain-derived neurotrophic factor (BDNF) in several brain regions. Furthermore, cell proliferation and adult hippocampal neurogenesis were assessed using Ki67 and Doublecortin. Voluntary wheel running induced increased anxiety in the openfield, elevated O-maze, and dark-light-box and higher levels of excreted corticosterone metabolites. We did not observe any antidepressant effect of running despite a significant increase of hippocampal neurogenesis and BDNF. These data are thus far the first to indicate that the effect of physical exercise in mice may be ambiguous. On one hand, the running-induced increase of neurogenesis and BDNF seems to be irrelevant in tests for depression-like behavior, at least in the present model where running activity exceeded previous reports. On the other hand, exercising mice display a more anxious phenotype and are exposed to higher levels of stress hormones such as corticosterone. Intriguingly, numbers of differentiating neurons correlate significantly with anxiety parameters in the openfield and dark-light-box. We therefore conclude that adult hippocampal neurogenesis is a crucial player in the genesis of anxiety.Hippocampus 06/2009; 20(3):364-76. · 5.18 Impact Factor -
Article: The puzzle box as a simple and efficient behavioral test for exploring impairments of general cognition and executive functions in mouse models of schizophrenia
[show abstract] [hide abstract]
ABSTRACT: Deficits in executive functions are key features of schizophrenia. Rodent behavioral paradigms used so far to find animal correlates of such deficits require extensive effort and time. The puzzle box is a problem-solving test in which mice are required to complete escape tasks of increasing difficulty within a limited amount of time. Previous data have indicated that it is a quick but highly reliable test of higher-order cognitive functioning.We evaluated the use of the puzzle box to explore executive functioning in five different mouse models of schizophrenia: mice with prefrontal cortex and hippocampus lesions, mice treated sub-chronically with the NMDA-receptor antagonist MK-801, mice constitutively lacking the GluA1 subunit of AMPA-receptors, and mice over-expressing dopamine D2 receptors in the striatum. All mice displayed altered executive functions in the puzzle box, although the nature and extent of the deficits varied between the different models. Deficits were strongest in hippocampus-lesioned and GluA1 knockout mice, while more subtle deficits but specific to problem solving were found in the medial prefrontal-lesioned mice, MK-801-treated mice, and in mice with striatal overexpression of D2 receptors.Data from this study demonstrate the utility of the puzzle box as an effective screening tool for executive functions in general and for schizophrenia mouse models in particular.Research Highlights►Mice with hippocampal lesions and GluA1 knockout mice displayed strong deficits in the puzzle box. ►Mice with medial prefrontal lesions displayed specific problem solving (executive) deficits. ►MK-801-treated mice and mice over-expressing D2 receptors exhibited subtle impairments in executive function. ►Validity of the puzzle box as a test for executive functions in schizophrenia models.Experimental Neurology. 227(1):42-52.
Top co-authors
Top Journals
- Experimental Neurology (2)
- Hippocampus (1)
- Synapse (1)
- Behavioural brain research (1)
- PLoS ONE (1)
Institutions
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2009–2013
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Central Institute of Mental Health
Mannheim, Baden-Wuerttemberg, Germany
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2010–2011
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Universität Heidelberg
- Central Institute of Mental Health
Heidelberg, Baden-Wuerttemberg, Germany
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