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H P Lipp

Publications and source records attributed to H P Lipp.

At least 37 records · Page 2Linked to original sources
PubMed2000

A GPS logger and software for analysis of homing in pigeons and small mammals.

A detailed analysis of homing in pigeons and small mammals has remained difficult because the paths of the animals could not be reconstructed precisely. Here, we describe a lightweight global position system (GPS) data logger (35 g including battery and casing; 40 x 68 x 18 mm) that records the flight of pigeons and the path of dogs with an accuracy of +/-12 m. With one battery, the logger runs in continuous mode (1 fix/s) for 3.5 h and in power-saving mode (1 fix/5 s) for about 16 h, and stores a maximum of 100,000 data points that are downloaded to a PC. A module of our public domain software WINTRACK permits a detailed numerical and graphical analysis of path geometry, phases of resting and moving, and path similarity. The device can be adapted to different species provided that satellite signals can be received reliably and that the loggers can be recovered. We expect it to be useful for testing hypotheses about pigeon homing, assessing natural spatial behavior and orientation of many species, and anticipate further miniaturization.

Animals↗
PubMed2000

The acallosal mouse strain I/LnJ: a putative model of ADHD?

ADHD has been sometimes associated to a defective interhemispheric cross-talk caused by hypoplasia of the corpus callosum. The inbred mouse strain I/LnJ shows total callosal agenesis with complete penetrance, and behavioral features which resemble ADHD. In conditioned learning tasks, as well as in paradigms of spontaneous behavior. I/LnJ mice, as compared to other inbred strains, show lower learning scores, impulsiveness, and significantly higher locomotor activity, albeit with considerable individual variations. In order to disentangle the influences of the genetic background from the effects of the callosal agenesis, we undertook crossing studies between I/LnJ and C57BL/6 mice, obtaining hybrids with missing corpus callosum. In comparison to normal C57BL/6 mice, acallosal hybrids exposed to a novel open-field showed a different locomotor pattern, with less short stops and more center crossing during the beginning of the session. In a metabolic mapping study, the tendency of acallosals to stay off the walls was found to be associated to lower 2-deoxyglucose uptake in the left striatum and cerebral cortex, while the number of short stops was correlated to the bilateral levels of 2-deoxyglucose uptake in the frontal and parietal cortex. The results hint at a right hemisphere dominance in impulsiveness and hyperactivity, boosted by the lack of callosal connections.

Agenesis of Corpus Callosum↗
PubMed2000

Genetic disruption of mineralocorticoid receptor leads to impaired neurogenesis and granule cell degeneration in the hippocampus of adult mice.

To dissect the effects of corticosteroids mediated by the mineralocorticoid (MR) and the glucocorticoid receptor (GR) in the central nervous system, we compared MR-/- mice, whose salt loss syndrome was corrected by exogenous NaCI administration, with GR-/- mice having a brain-specific disruption of the GR gene generated by the Cre/loxP-recombination system. Neuropathological analyses revealed a decreased density of granule cells in the hippocampus of adult MR-/- mice but not in mice with disruption of GR. Furthermore, adult MR-/- mice exhibited a significant reduction of granule cell neurogenesis to 65% of control levels, possibly mediated by GR due to elevated corticosterone plasma levels. Neurogenesis was unaltered in adult mice with disruption of GR. Thus, we could attribute long-term trophic effects of adrenal steroids on dentate granule cells to MR. These MR-related alterations may participate in the pathogenesis of hippocampal changes observed in ageing, chronic stress and affective disorders.

Animals↗
PubMed2000

Dissecting the behaviour of transgenic mice: is it the mutation, the genetic background, or the environment?

Increasingly sophisticated and precise molecular genetic tools are applied to mice in order to study the cellular mechanisms underlying higher brain functions, including learning and memory. However, several studies have produced unclear or conflicting results. One reason for this is that performance in the behavioural tests used to assess learning and memory is influenced by various non-cognitive phenomena and can thus easily be affected by mutations through mechanisms unrelated to memory function. We conducted principal component analysis on data from 3003 mice tested using a standardized protocol to demonstrate this for the Morris swimming navigation test, one of the most widely used paradigms to assess memory and hippocampal function. In addition, we present a meta-analysis showing that genetic background and environment alone produce sufficient variation to span the range of most, if not all, behavioural variables and can thus easily mask or fake mutation effects if genetic studies are not designed properly. We suggest that the chance of obtaining useful results is maximized if behavioural deficits are differentiated by combining complementary behavioural protocols and by analysing multiple complementary parameters in each of them. Mutation effects must be contrasted statistically against the influences of genetic background and environment. In many situations, this is most efficiently achieved if (i) mutations are backcrossed to and maintained in one or (preferably) two well-characterized, commonly available inbred strains and (ii) if mutant and wild-type littermates are analysed on a hybrid or mixed genetic background, that is in F1 or F2 generations derived from the inbred stocks.

Animals↗
PubMed1999

Deletion of the ryanodine receptor type 3 (RyR3) impairs forms of synaptic plasticity and spatial learning.

Deletion of the ryanodine receptor type 3 (RyR3) results in specific changes in hippocampal synaptic plasticity, without affecting hippocampal morphology, basal synaptic transmission or presynaptic function. Robust long-term potentiation (LTP) induced by repeated, strong tetanization in the CA1 region and in the dentate gyrus was unaltered in hippocampal slices in vitro, whereas weak forms of plasticity generated by either a single weak tetanization or depotentiation of a robust LTP were impaired. These distinct physiological deficits were paralleled by a reduced flexibility in re-learning a new target in the water-maze. In contrast, learning performance in the acquisition phase and during probe trial did not differ between the mutants and their wild-type littermates. In the open-field, RyR3(-/-) mice displayed a normal exploration and habituation, but had an increased speed of locomotion and a mild tendency to circular running. The observed physiological and behavioral effects implicate RyR3-mediated Ca(2+) release in the intracellular processes underlying spatial learning and hippocampal synaptic plasticity.

Animals↗
PubMed1999

Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the beta-amyloid-precursor protein.

We previously have reported corpus callosum defects in transgenic mice expressing the beta-amyloid precursor protein (betaAPP) with a deletion of exon 2 and at only 5% of normal levels. This finding indicates a possible involvement of betaAPP in the regulation or guidance of axon growth during neural development. To determine to what degree the betaAPP mutation interacts with genetic background alleles that predispose for forebrain commissure defects in some mouse lines, we have assessed the size of the forebrain commissures in a sample of 298 mice. Lines with mixed genetic background were compared with congenic lines obtained by backcrossing to the parental strains C57BL/6 and 129/SvEv. Mice bearing a null mutation of the betaAPP gene also were included in the analysis. We show that, independently of genetic background, both lack and underexpression of betaAPP are associated with reduced brain weight and reduced size of forebrain commissures, especially of the ventral hippocampal commissure. In addition, both mutations drastically increase the frequency and severity of callosal agenesis and hippocampal commissure defects in mouse lines with 129/SvEv or 129/Ola background.

Amyloid beta-Protein Precursor↗
PubMed1999

Left-hemispheric superiority for visuospatial orientation in homing pigeons.

To test for lateralisation of visuospatial orientation during homing, pigeons who had binocularly learned the homeward route from remote release sites were tested monocularly on either their left or their right eye for homing performance. In two experiments with three different release sites, birds using their right eye showed considerably better homing performance. If sun compass information was available, there was no difference in the direction of vanishing. Without this information, a difference between pigeons using their left or right eye emerged. Results show that visuospatial orientation in birds can be lateralised in favour of the left brain hemisphere and lend further support to the view that vision is important for pigeons homing on a familiar route. Cognitive mechanisms which might account for the observed pattern of lateralisation are discussed.

Animals↗
PubMed1999

No hippocampal neuron or synaptic bouton loss in learning-impaired aged beta-amyloid precursor protein-null mice.

Aged beta-amyloid precursor protein-null mice were used to investigate the relationship between beta-amyloid precursor protein, hippocampal neuron and synaptic bouton number, and cognitive function. Learning and memory performance of aged beta-amyloid precursor protein-null mice and age-matched controls were assessed in the Morris water maze. Beta-amyloid precursor protein-null mice demonstrated impaired task acquisition as measured by significantly longer swim path lengths, a higher percentage of failed trials, and more frequent thigmotaxis behavior than controls. In a subsequent probe trial, beta-amyloid precursor protein-null mice spent significantly less time in the old goal quadrant, and made fewer crossings over the old platform location than did controls. No differences in motor or visual skills were observed which could account for the performance differences. In light of these findings and previous evidence for a role of beta-amyloid precursor protein in neuronal maintenance and synaptogenesis, we pursued the hypothesis that the learning impairment of beta-amyloid precursor protein-null mice may be a reflection of differences in neuron or synaptophysin-positive presynaptic bouton number. Thus, unbiased stereological analysis was used to estimate neuron and synaptic bouton number in dentate gyrus and hippocampal CA1 of the behaviorally characterized mice. No difference in neuron or synaptophysin-positive presynaptic bouton number was found between the beta-amyloid precursor protein-null mice and age-matched controls. Our results suggest that the learning impairment of beta-amyloid precursor protein-null mice is not mediated by a loss of hippocampal neurons or synaptic boutons.

Aging↗
PubMed1999

Essential role for TrkB receptors in hippocampus-mediated learning.

Brain-derived neurotrophic factor (BDNF) and its receptor TrkB regulate both short-term synaptic functions and long-term potentiation (LTP) of brain synapses, raising the possibility that BDNF/TrkB may be involved in cognitive functions. We have generated conditionally gene targeted mice in which the knockout of the trkB gene is restricted to the forebrain and occurs only during postnatal development. Adult mutant mice show increasingly impaired learning behavior or inappropriate coping responses when facing complex and/or stressful learning paradigms but succeed in simple passive avoidance learning. Homozygous mutants show impaired LTP at CA1 hippocampal synapses. Interestingly, heterozygotes show a partial but substantial reduction of LTP but appear behaviorally normal. Thus, CA1 LTP may need to be reduced below a certain threshold before behavioral defects become apparent.

Animals↗
PubMed1998

An automated system, based on microchips, for monitoring individual activity in wild small mammals.

A new battery-operated system based on microchips has been developed for detecting free-moving, wild small mammals. An electronic identification unit connected to a portable data-logger can simultaneously accommodate up to eight detector antennae, which are positioned in the habitat of the species under study. The system can operate even in extreme weather conditions and has the capacity to distinguish and record individual mammals entering burrows or visiting artificial feeding stations. Detection events are stored in a data-logger and subsequently can be edited and analysed by many common software packages. A pilot study tested the system by monitoring the visits of three species of small mammals to artificial feeding stations. Further possible applications are discussed.

Animal Identification Systems↗
PubMed1998

Expression of the axon growth-related neural adhesion molecule TAG-1/axonin-1 in the adult mouse brain.

TAG-1/axonin-1 is a neuronal cell adhesion molecule of the immunoglobulin superfamily. It is predominantly expressed during neural development and has been reported to be involved in axonal growth and pathfinding. Here, the expression of TAG-1/axonin-1 was investigated anatomically in the adult mouse brain by in situ hybridization using digoxigenin-labeled cRNA probes. Low levels of TAG-1/axonin-1 could be detected in cerebellar granule cells, in tufted and mitral cells of the olfactory bulb, and in pyramidal cells of area CA1 and CA3 of the hippocampus. We suspect that the expression of TAG-1/axonin-1 in these structures of the adult brain may serve neural plasticity.

Animals↗
PubMed1998

A 2-year longitudinal study of swimming navigation in mice devoid of the prion protein: no evidence for neurological anomalies or spatial learning impairments.

Uncontrolled accumulation of a conformationally distorted protein (PrP(Sc)) is supposed to be the pathological process leading to spongiform encephalopathy. Targeted disruptions of the Prn-P gene in the mouse have resulted in animals that did not show anomalies in spatial and avoidance learning and were resistant to experimental infections. However, another Prn-P knockout mouse was reported to show ataxia and Purkinje cell degeneration developing after 70 weeks of age. In this study the initial observations are confirmed on swimming navigation of PrP-null mutant mice using an enlarged sample of 58 mice. A representative subsample of 16 mice was then followed up for their ability of swimming navigation up to an age of two years (104 weeks). Surviving PrP-null mutants (n = 4) and controls (n = 6) did not differ in any measure, nor were there indications of ataxia and Purkinje cell degeneration. It was concluded that the PrP-knockout mice used by Büeler et al. were probably normal with respect to aging processes and that resistance to scrapie is not necessarily paid for by late neuronal degeneration. The reasons for the discrepancy between different knockout experiments require experimental clarification, however.

Animals↗
PubMed1998

Neurobehavioral development, adult openfield exploration and swimming navigation learning in mice with a modified beta-amyloid precursor protein gene.

The processing of beta-amyloid precursor protein (betaAPP) and its metabolites plays an important role in the pathogenesis of Alzheimer's disease (AD) and Down's syndrome. The authors have reported elsewhere that a targeted mutation resulting in low expression of a shortened betaAPP protein (betaAPP(delta/delta)) entails reduced learning abilities. Here the authors investigate whether these effects were caused by postnatal developmental actions of the altered protein. The authors examined 35 mice carrying the betaAPP(delta/delta) mutation for somatic growth and sensorimotor development during the first 4 postnatal weeks (pw) and compared them with 31 wildtype litter-mates. Thereafter, the same mice were tested at about 10 weeks of age for openfield behavior and for swimming navigation learning. Mutant mice showed both transient and long-lasting deficits in development. Body weight deficit started to emerge at postnatal day (pd) 12, peaked with a 15.1% deficit at pd 27 and lasted until pw 33-37. Significant transient deficits in mutant mice during sensorimotor development were observed in three time windows (pd 3-10, pd 11-19 and pd 20-27), long-lasting effects, manifest at pw 8-12 and pw 33-37, emerged at any of the three periods. In the adult mice, exploratory activity of betaAPP mutants in the openfield arena was severely reduced. In the Morris water maze task, mutant mice showed moderate escape performance deficits during the acquisition period but no impairment in spatial memory. The authors conclude that a defective betaAPP gene impairs postnatal somatic development, associated with transient as well as long-lasting neurobehavioral retardation and muscular weakness. Comparison with earlier data suggests that early postnatal handling may attenuate some of the non-cognitive performance deficits in the water maze. Further, the manifestation and time course of behavioral yet not neuropathological symptoms in betaAPP mutant mice resemble in some aspects those of the human Down's syndrome.

Adult↗
PubMed1998

Increased asymmetries in 2-deoxyglucose uptake in the brain of freely moving congenitally acallosal mice.

To investigate the role of the corpus callosum in the expression of functional brain asymmetries, we compared left and right uptake of [14C]2-deoxyglucose in 43 brain regions measured in 10 C57B1/6 mice with a normal corpus callosum and in 12 congenitally acallosal mice, after 45 min of free activity in a novel, large open-field arena. The metabolic patterns across the brain appeared to be similar in the two groups of mice, as well as the average direction of asymmetry in tracer incorporation, which was higher at right in most of the brain regions for both acallosals and controls. However, the direction of the metabolic asymmetries of any given region was not consistent across individual animals. The largest asymmetries were found in the central auditory nuclei in both groups of mice, with extreme values in some acallosals. Significantly larger asymmetries were found in acallosal mice for the brain and the cortex as a whole, as well as for the lateral geniculate and pretectal nuclei, the olfactory tubercles, and retrosplenial, infrarhinal and perirhinal cortices. The metabolic asymmetries of the thalamic sensory nuclei were correlated with the asymmetries of the corresponding sensory cortical fields in the acallosal, but not in control mice. On the other hand, asymmetries of the cortical regions were largely intercorrelated in control mice, resulting in a general activation of one hemisphere over the other, while in acallosals they were more independent, resulting in a "patchy" pattern of cortical asymmetries. These results suggest that callosal agenesis, combined with the occurrence of ipsilateral Probst bundles, leads to a loss of co-ordination in the activation of different sensory and motor areas. The impaired co-ordination might then be distributed through cortico-subcortical loops, resulting in larger asymmetries throughout the brain. Thus, a normal corpus callosum appears to balance and synchronize metabolic brain activity, perhaps by smoothing the effects of asymmetrically activated ascending systems.

Agenesis of Corpus Callosum↗
PubMed1998

Genetically modified mice and cognition.

Cognition in transgenic and knockout mice is preferentially assessed by spatial learning in the Morris water maze. Awareness is growing, however, that the putative cognitive deficits observed using such a paradigm may be biased by the genetic background and behavioral peculiarities of the specific animals used. Recent progress in cognitive research includes new behavioral tests and refined analysis of performance impairments. Advances in our understanding of memory and learning are being made possible through use of transgenic rescue of disrupted genes, inducible and reversible gene targeting in selected brain regions, and single-cell recordings of hippocampal place cells in mutant mice.

Animals↗
PubMed1998

Increased flexibility and selectivity in spatial learning of transgenic mice ectopically expressing the neural cell adhesion molecule L1 in astrocytes.

The expression of the neural cell adhesion molecule L1 is altered by neuronal activity and promotes neurite outgrowth in vitro. To study the effects of L1 on learning and synaptic plasticity, transgenic mice have been created which express L1 ectopically in glial fibrillary acidic protein (GFAP) expressing astrocytes. Ninety mice, including GFAP-L1-transgenic mice from two genetic backgrounds and their littermates, were tested for swimming navigation learning in the Morris water maze according to a standardized protocol. While learning the position of an invisible target platform and also relearning its position after relocation, GFAP-L1-transgenic mice spent a greater fraction of their swim time in the target quadrant. Moreover, they showed a more rapid improvement of escape performance during the first day of training. Factor analysis revealed that this difference in swimming pattern could not be explained by non-cognitive factors. Factor analysis also revealed that, during a probe trial, the GFAP-L1-transgenic mice spent comparatively less time in the old target quadrant than predicted by the increased searching they had shown during acquisition learning. Hence, ectopic expression of L1 by astrocytes in mice appears to be linked to a factor which increases behavioural flexibility and selectivity while learning and relearning, but concomitantly may lead to a relative reduction of spatial retention.

Animals↗
PubMed1997

Defective limbic system in mice lacking the tailless gene.

The gene tailless is a member of the superfamily of genes that encode transcription factors of the ligand-activated nuclear receptor type, and is expressed in the invertebrate and vertebrate brain. In mice, its transcripts are restricted to the periventricular zone of the forebrain, the site of origin of neurons and glia. Here we use homologous recombination to generate mice that lack a functional tailless protein. Homozygous mutant mice are viable at birth, indicating that tailless is not required for prenatal survival; however, adult mutant mice show a reduction in the size of rhinencephalic and limbic structures, including the olfactory, infrarhinal and entorhinal cortex, amygdala and dentate gyrus. Both male and female mice are more aggressive than usual and females lack normal maternal instincts. These animals therefore enable a molecular approach to be taken towards understanding the genetic architecture and morphogenesis of the forebrain.

Animals↗