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The neurotransmitter serotonin plays a key role in the control of aggressive behaviour. While so far most studies have investigated variation in serotonin levels, a recently created tryptophan hydroxylase 2 (Tph2) knockout mouse model allows studying effects of complete brain serotonin deficiency. First studies revealed increased aggressiveness in homozygous Tph2 knockout mice in the context of a resident-intruder paradigm. Focussing on females, this study aimed to elucidate effects of serotonin deficiency on aggressive and non-aggressive social behaviours not in a test situation but a natural setting. For this purpose, female Tph2 wildtype (n = 40) and homozygous knockout mice (n = 40) were housed with a same-sex conspecific of either the same or the other genotype in large terraria. The main findings were: knockout females displayed untypically high levels of aggressive behaviour even after several days of co-housing. Notably, in response to aggressive knockout partners, they showed increased levels of defensive behaviours. While most studies on aggression in rodents have focussed on males, this study suggests a significant involvement of serotonin also in the control of female aggression. Future research will show, whether the observed behavioural effects are directly caused by the lack of serotonin or by potential compensatory mechanisms.

The time of dominance rank acquisition is a crucial phase in male life history that often affects reproductive success and hence fitness. Hormones such as testosterone and glucocorticoids can influence as well as be affected by this process. At the same time, hormone concentrations can show large individual variation. The extent to which such variation is repeatable, particularly in dynamic social settings, is a question of current interest. The aim of the present study was therefore to investigate how dominance rank and individual differences contribute to variance in hormone concentrations during male rank acquisition in a complex social environment. For this purpose, dominance rank as well as baseline testosterone, baseline cortisol, and cortisol responsiveness after exposure to a novel environment were determined in colony-housed guinea pig males from late adolescence through adulthood. Hormone-dominance relationships and repeatability of hormone measures beyond their relation to rank were assessed. There was a significant positive relationship between baseline testosterone and rank, but this link became weaker with increasing age. Baseline cortisol or cortisol responsiveness, in contrast, were not significantly related to dominance. Notably, all three endocrine parameters were significantly repeatable independent of dominance rank from late adolescence through adulthood. Baseline testosterone and cortisol responsiveness showed a significantly higher repeatability than baseline cortisol. This suggests that testosterone titres and cortisol responsiveness represent stable individual attributes even under complex social conditions.

Automated touchscreen techniques find increasing application for the assessment of cognitive function in rodents. However, hardly anything is known about the potential impact of touchscreen-based training and testing procedures on the animals under investigation. Addressing this question appears particularly important in light of the long and intensive training phases required for most of the operant tasks. Against this background, we here investigated the influence of regular touchscreen training on hormones and behaviour of mice. Faecal corticosterone metabolites (FCMs), reflecting corticosterone levels around the time of treatment, were significantly increased in touchscreen-trained mice, even one week after the training phase was already terminated. Such an effect was not detected on baseline FCMs. Thus, regular touchscreen training can be assumed to cause long-term effects on hypothalamus-pituitary-adrenal axis activity. Furthermore, anxiety-like behaviour was increased in touchscreen-trained mice two weeks after the end of the training phase. Traditionally, this would be interpreted as a negative influence of the training procedure on the animals’ affective state. Yet, we also provide two alternative explanations, taking the possibility into account that touchscreen training might have enriching properties.

This paper gives an overview about all activities performed within a common project between industrial and academic partners to define clean room concepts for the first worldwide high volume semiconductor front end facility IFD for 300 mm power semiconductors. The investigation within this study is the base for the 300 mm container strategy resulting in new innovative manufacturing and automation concepts.

Based on the concept that experience-dependent memory may be biased by affective state at the time of learning, the affective bias test represents a novel approach for the assessment of emotions in animals. The task uses a within-subjects study design, where animals encounter two independent discrimination tasks on separate test days and learn that digging in one out of two substrates is rewarded with food. While one pair of substrates is associated with an affective manipulation, the other functions as a neutral control. Potential affective biases are then quantified by a preference test in which both initially rewarded substrates are tested against each other. Since the test was originally developed for the work with rats, the aims of the present study were (1) to translate the paradigm from rats to mice, and (2) to investigate the impact of an environmental enrichment on affective state in male C57BL/6J mice. For this reason, two control groups were included in the study that served to validate the overall testing procedure. One control group experienced equal absolute reward values for both rewarded substrates, assuming that this would prevent a substrate preference. In the second control group, we tripled the reward for one substrate, hypothesizing that mice would bias their choice towards this higher rewarded substrate in the preference test. Indeed, animals of the first control group did not show any substrate preference, while subjects of the second control group preferred the substrate associated with the high reward. Thus, mice were able to learn the association between absolute reward value and respective substrate, indicating that the affective bias test has the potential to work in mice. Besides these control groups, a third group was implemented in the study: As for the first control group, the absolute reward value was the same for both rewarded substrates, but in addition to that, affective state at the time of learning was modified for one substrate by subjecting mice to a highly enriched cage directly after testing. Since enrichment is known to influence the behaviour and physiology of rodents mostly in a positive way, we expected to observe a preference for the substrate associated with the enriched cage. However, in contrast to our expectations, mice did not show any substrate preference, suggesting that the additional enrichment provided in the enriched cage was probably not sufficient to induce measurable changes in an affective state.

The translational assessment of mechanisms underlying cognitive functions using touchscreen-based approaches for rodents is growing in popularity. In these paradigms, daily training is usually accompanied by extended food restriction to maintain animals' motivation to respond for rewards. Here, we show a transient elevation in stress hormone levels due to food restriction and touchscreen training, with subsequent adaptation effects, in fecal corticosterone metabolite concentrations, indicating effective coping in response to physical and psychological stressors. Corticosterone concentrations of experienced but training-deprived mice revealed a potential anticipation of task exposure, indicating a possible temporary environmental enrichment-like effect caused by cognitive challenge. Furthermore, the analyses of immediate early gene (IEG) immunoreactivity in the hippocampus revealed alterations in Arc, c-Fos and zif268 expression immediately following training. In addition, BDNF expression was altered as a function of satiation state during food restriction. These findings suggest that standard protocols for touchscreen-based training induce changes in hippocampal neuronal activity related to satiation and learning that should be considered when using this paradigm.

Besides being recognized as a potential welfare indicator, play behaviour has long been considered to have immediate and/or long-term benefits. In particular, it has been suggested that in play animals learn to cope physically and emotionally with unexpected events. Given that the propensity to play varies greatly between conspecific individuals, such interindividual variability in playfulness may be associated with differences in the animals' future behaviour, a prediction that has rarely been tested. To investigate whether different levels of playfulness in juvenility indeed coincide with behavioural differences in later life, 30 female C57BL/6J mice were subjected to the following series of behavioural observations and tests: (1) quantification of juvenile play behaviour; (2) behavioural testing in paradigms that assess anxiety-like behaviour and exploratory locomotion in an unfamiliar environment; and (3) observation of spontaneous behaviour in the familiar home cage environment. Surprisingly, a high level of juvenile playfulness was predictive of high levels of state anxiety and low levels of exploratory locomotion in later life. While this relationship existed already in adolescence, it became even more prominent in adulthood. By contrast, no substantial differences between playful and less playful mice were found with respect to home cage behaviour. While these findings may reflect better coping abilities in novel and dangerous environments in those mice that played the most during juvenility, they may also argue for the existence of different types of mice. Thus, despite genetic homogeneity and identical housing environments, preferences for either local or global use of space were observed that indicate the emergence of individuality. Concerning animal welfare, our findings suggest that play may constitute a plausible welfare indicator at the population level, but is probably less meaningful for the individual.

Phenotypic plasticity allows individuals to adjust traits to the environment. Whether long-term adjustments of the phenotype occur during later life stages is largely unknown. To address this question, we examined whether hormonal phenotypes that are shaped by the environment during adolescence can still be reshaped in full adulthood. For this, guinea pig males were either housed in mixed-sex colonies or in heterosexual pairs. In adulthood, males were individually transferred to pair housing with a female. This way, a social niche transition was induced in colony-housed males, but not in pair-housed males. Before transfer, corresponding to findings in adolescence, adult colony-housed males showed significantly higher baseline testosterone levels and lower cortisol responsiveness than pair-housed males. One month after transfer, the hormonal phenotype of colony-housed males was changed towards that of pair-housed males: animals showed comparable baseline testosterone levels and cortisol responsiveness was significantly increased in colony-housed males. This endocrine readjustment builds the basis for an adaptive behavioural tactic in the new social situation. Thus, an adaptive change of the behavioural phenotype may still occur in adulthood via modification of underlying mechanisms. This suggests a greater role for developmental plasticity in later life stages than is commonly presumed.

Recently, a discussion about the reproducibility of results from behavioural phenotyping experiments has emerged. A huge emphasis has therefore been put on the identification of those factors that might limit the reproducibility of behavioural data. As a comprehensive phenotypic characterisation can involve testing of the same animal repeatedly over a specific time period, the aim of the present study was to systematically investigate effects of two potentially confounding variables, age of the animals and test experience. For this purpose, the behaviour of 48 male C57BL/6 J mice of two different ages (9 vs. 13 weeks) was assessed in a battery of common behavioural tests measuring anxiety-like and exploratory behaviour (Elevated Plus Maze, Dark-Light test, Open Field test, Novel Cage test). While half of the mice of each age group was naive to the test battery, the other half had experienced the same tests before. Besides main effects of both age and test experience on anxiety-like and exploratory behaviour, the analysis also revealed profound interactions between these factors. More precisely, an effect of age was apparent in experienced but not in naive mice. Furthermore, the effect of previous test experience was more pronounced in older than in younger mice. These findings clearly demonstrate that experimental factors, such as age and test experience, can influence behavioural data not just additively, but also in a complex, interactive way. To provide robust and reproducible results, it is thus fundamental to consider such factors systematically in the study design.

The scientific community is increasingly concerned with cases of published “discoveries” that are not replicated in further studies. The field of mouse behavioral phenotyping was one of the first to raise this concern, and to relate it to other complicated methodological issues: the complex interaction between genotype and environment; the definitions of behavioral constructs; and the use of the mouse as a model animal for human health and disease mechanisms. In January 2015, researchers from various disciplines including genetics, behavior genetics, neuroscience, ethology, statistics and bioinformatics gathered in Tel Aviv University to discuss these issues. The general consent presented here was that the issue is prevalent and of concern, and should be addressed at the statistical, methodological and policy levels, but is not so severe as to call into question the validity and the usefulness of model organisms as a whole. Well-organized community efforts, coupled with improved data and metadata sharing, were agreed by all to have a key role to play in identifying specific problems and promoting effective solutions. As replicability is related to validity and may also affect generalizability and translation of findings, the implications of the present discussion reach far beyond the issue of replicability of mouse phenotypes but may be highly relevant throughout biomedical research.

Over the past years, certain “vulnerability genes” have been identified that play a key role in the development of mood and anxiety disorders. In particular, a low-expressing variant of the human serotonin transporter (5-HTT) gene has been described that renders individuals more susceptible to adverse experience and hence to the development of psychiatric diseases. However, some authors have recently argued that lower 5-HTT expression not only increases vulnerability to adverse experiences, but also enhances susceptibility to beneficial experiences, thus promoting phenotypic plasticity. The aim of the present study was to assess the effects of 5-HTT expression on susceptibility to beneficial experience in a hypothesis-driven experimental approach. Using a well-established rodent model for the human polymorphism, male heterozygous 5-HTT knockout (HET) and 5-HTT wildtype (WT) mice were either provided with the beneficial experience of cohabitation with a female (mating experience) or kept as naive controls in single-housing conditions. Following the experimental treatment, they were tested for their anxiety-like behaviour and exploratory locomotion in three widely used behavioural tests. Interestingly, while cohabitation reduced anxiety-like behaviour and increased exploratory locomotion in the open field test in HET mice, it did not affect WT mice, pointing to a genotype-dependent susceptibility to the beneficial experience. Thus, our results might support the view of the low expressing version of the 5-HTT gene as a “plasticity” rather than a “vulnerability” variant.

Several prospective studies indicated perinatal hypoxia as risk factor for psychiatric disorders like schizophrenia. It is thought that hypoxia prior to or during birth may contribute to alterations leading to the protracted clinical manifestation during young adulthood. However, only a small fraction of children with a history of perinatal hypoxia develop later psychotic symptoms, therefore it is not known if hypoxia alone is sufficient to trigger long-term behavioral changes. Here we exposed C57BL/6 mice from postnatal day 3–7 (P3–P7) to two established paradigms of chronic mild hypoxia (10% ambient O2), intermittent and continuous. Subsequently, mice were analysed during young adult stages using several basic behavioral tests. Previous studies demonstrated severe, but only transient, cortical damage in these paradigms; it is not clear, if these reversible morphological changes are accompanied by long-term behavioral effects. We found that neither intermittent nor continuous perinatal hypoxia induced long-term behavioral alterations. This may be due to the high regenerative capacity of the perinatal brain. Other possibilities include a potential resistance to perinatal hypoxia of the mouse strain used here or a level of hypoxia that was insufficient to trigger significant behavioral changes. Therefore, our data do not exclude a role of perinatal hypoxia as risk factor for psychiatric disorders. They rather suggest that either other, more severe hypoxic conditions like anoxia, or the presence of additional factors (as genetic risk factors) are necessary for generating long-term behavioral abnormalities.

Physical exercise is known to exert various beneficial effects on brain function and bodily health throughout life. In biomedical research, these effects are widely studied by introducing running wheels into the cages of laboratory rodents. Yet, although rodents start to run in the wheels immediately, and perform wheel-running excessively on a voluntary basis, the biological significance of wheel-running is still not clear. Here, we review the current literature on wheel-running and discuss potentially negative side-effects that may give cause for concern. We particularly emphasize on analogies of wheel-running with stereotypic and addictive behavior to stimulate further research on this topic.

Although preconceptional and periconceptional maternal stress is a recognized risk factor for offspring neurodevelopmental disturbances, less is known about the relevance of paternal exposures. These have hitherto been investigated mainly with respect to substance-induced impairment in the progeny. In recent years, experiential influences on offspring have come into focus through growing insight into epigenetic mechanisms such as nongenetic modes of transmission. The effect of chronic and/or early manipulations in males has been studied but much less is known about the potential impact of singular manipulations in older individuals. We investigated the influence of a strong stressor exposure, reminiscent of a traumatic event, in adult male mice on offspring behavior. Male mice, 6 weeks of age, received a strong footshock and were mated to naïve females several weeks later. Male and female offspring were investigated in a variety of tests for anxiety-like and depression-like behaviors. In addition, bodyweight development was assessed. Although we did not observe any alterations in anxiety-like and depressive-like behavioral indices, we recorded reduced bodyweight development in the female offspring. Our data emphasize the relevance of sex as a (co)determinant of outcomes in the wake of parental manipulations. They further suggest that the window of vulnerability for the induction of patrilinear effects might be wider than that currently assumed.

Behavioural performance of mice - group comparison between the tests rounds

Semiconductor manufacturing is a highly complex process, with a high need for process control, but equally important are effective methods for contamination control. Methods for detection of airborne and surface molecular contaminants were enhanced to meet the increasing requirements for future More Moore and More than Moore applications. Improved qualitative and quantitative contamination analysis methods of organic and inorganic compounds allow exact monitoring of contamination in front- as well as back-end processes. By the use of state-of-the-art analytical systems combined with validated analytical procedures and advanced sample preparation techniques contamination analytical results with higher reproducibility and reliability are being ensured.

In mammals, weaning constitutes an important phase in the progression to adulthood. It comprises the termination of suckling and is characterized by several changes in the behaviour of both mother and offspring. Furthermore, numerous studies in rodents have shown that the time point of weaning shapes the behavioural profile of the young. Most of these studies, however, have focused on 'early weaning', while relatively little work has been done to study 'late weaning' effects. The aim of the present study was therefore to explore behavioural effects of 'late weaning', and furthermore to gain insights into modulating effects of weaning age on the consistency of behavioural expressions over time. In total, 25 male and 20 female C57BL/6J mice, weaned after three (W3) or four (W4) weeks of age, were subjected to a series of behavioural paradigms widely used to assess anxiety-like behaviour, exploratory locomotion, and nest building performance. Behavioural testing took place with the mice reaching an age of 20 weeks and was repeated eight weeks later to investigate the stability of behavioural expressions over time. At the group level, W4 mice behaved less anxious and more explorative than W3 animals in the Open Field and Novel Cage, while anxiety-like behaviour on the Elevated Plus Maze was modulated by a weaning-age-by-sex interaction. Furthermore, weaning age shaped the degree of behavioural stability over time in a sex-specific way. While W3 females and W4 males displayed a remarkable degree of behavioural stability over time, no such patterns were observed in W3 males and W4 females. Adding to the existing literature, we could thus confirm that effects of weaning age do indeed exist when prolonging this phase, and were furthermore able to provide first evidence for the impact of weaning age and sex on the consistency of behavioural expressions over time.

A novel inspection technology for detection of thin polymer layers, deposited on structured silicon wafer surfaces, has been developed. The labeling of polymer residues with fluorophore combined with the subsequent examination under a fluorescence microscope enables a non-destructive detection of amorphous and semi-crystalline polymers and polymer residues on wafer substrates.

Stereotypies are repetitive, unvarying, apparently purposeless behavioural patterns. They develop in animals kept in barren environments and are highly prevalent in laboratory mice ( Mus musculus ), yet their underlying mechanisms have remained elusive. In humans, stereotypies are associated with several psychiatric disorders and are thought to reflect dysfunction of inhibition of motor programs mediated by the corticostriatal circuitry, resulting in recurrent perseveration (=inappropriate repetition of behavioural responses). Several studies in captive animals of different species have reported a correlation between stereotypy performance and perseverative behaviour, indicating a similar dysfunction. To examine whether stereotypies in mice correlate with recurrent perseveration and whether they are causally related, we raised 40 female ICR CD-1 mice in either barren or enriched cages from three to either six or 16 weeks of age (2 × 2 factorial design) and assessed stereotypic behaviour in the home cage and recurrent perseveration on a two-choice guessing task. Enrichment significantly reduced stereotypic behaviour both at six and 16 weeks of age and recurrent perseveration increased with age. Although enriched housing reduced the number of repetitions in the guessing task significantly, there was no clear evidence for an effect on recurrent perseveration, and recurrent perseveration did not correlate positively with stereotypy level. These findings indicate either that this test did not measure recurrent perseveration or that cage stereotypies in these mice do not reflect behavioural disinhibition as measured by recurrent perseveration.

It is widely believed that environmental standardization is the best way to guarantee reproducible results in animal experiments. However, mounting evidence indicates that even subtle differences in laboratory or test conditions can lead to conflicting test outcomes. Because experimental treatments may interact with environmental conditions, experiments conducted under highly standardized conditions may reveal local 'truths' with little external validity. We review this hypothesis here and present a proof of principle based on data from a multilaboratory study on behavioral differences between inbred mouse strains. Our findings suggest that environmental standardization is a cause of, rather than a cure for, poor reproducibility of experimental outcomes. Environmental standardization can contribute to spurious and conflicting findings in the literature and unnecessary animal use. This conclusion calls for research into practicable and effective ways of systematic environmental heterogenization to attenuate these scientific, economic and ethical costs.

Several studies on both humans and animals reveal benefits of physical exercise on brain function and health. A previous study on TgCRND8 mice, a transgenic model of Alzheimer's disease, reported beneficial effects of premorbid onset of long-term access to a running wheel on spatial learning and plaque deposition. Our study investigated the effects of access to a running wheel after the onset of Abeta pathology on behavioural, endocrinological, and neuropathological parameters. From day 80 of age, the time when Abeta deposition becomes apparent, TgCRND8 and wildtype mice were kept with or without running wheel. Home cage behaviour was analysed and cognitive abilities regarding object recognition memory and spatial learning in the Barnes maze were assessed. Our results show that, in comparison to Wt mice, Tg mice were characterised by impaired object recognition memory and spatial learning, increased glucocorticoid levels, hyperactivity in the home cage and high levels of stereotypic behaviour. Access to a running wheel had no effects on cognitive or neuropathological parameters, but reduced the amount of stereotypic behaviour in transgenics significantly. Furthermore, wheel-running was inversely correlated with stereotypic behaviour, suggesting that wheel-running may have stereotypic qualities. In addition, wheel-running positively correlated with plaque burden. Thus, in a phase when plaques are already present in the brain, it may be symptomatic of brain pathology, rather than protective. Whether or not access to a running wheel has beneficial effects on Alzheimer-like pathology and symptoms may therefore strongly depend on the exact time when the wheel is provided during development of the disease.

From a behavioural biologist's point of view, we argue: (1) The study of resilience in animals should not be restricted to neuronal mechanisms. Rather, questions of ontogeny, function, and evolution also should be addressed to achieve a comprehensive understanding. (2) Implementing new paradigms from animal welfare research in studies of resilience would allow an assessment of appraisal styles in animals.

Behavioral profiles are influenced by both positive and negative experiences as well as the genetic disposition. Traditionally, accumulating adversity over lifetime is considered to predict increased anxiety-like behavior (“allostatic load”). The alternative “mismatch hypothesis” suggests increased levels of anxiety if the early environment differs from the later-life environment. Thus, there is a need for a whole-life history approach to gain a deeper understanding of how behavioral profiles are shaped. The aim of this study was to elucidate the effects of life history on the behavioral profile of mice varying in serotonin transporter (5-HTT) genotype, an established mouse model of increased anxiety-like behavior. For this purpose, mice grew up under either adverse or beneficial conditions during early phases of life. In adulthood, they were further subdivided so as to face a situation that either matched or mismatched the condition experienced so far, resulting in four different life histories. Subsequently, mice were tested for their anxiety-like and exploratory behavior. The main results were: (1) Life history profoundly modulated the behavioral profile. Surprisingly, mice that experienced early beneficial and later escapable adverse conditions showed less anxiety-like and more exploratory behavior compared to mice of other life histories. (2) Genotype significantly influenced the behavioral profile, with homozygous 5-HTT knockout mice displaying highest levels of anxiety-like and lowest levels of exploratory behavior. Our findings concerning life history indicate that the absence of adversity does not necessarily cause lower levels of anxiety than accumulating adversity. Rather, some adversity may be beneficial, particularly when following positive events. Altogether, we conclude that for an understanding of behavioral profiles, it is not sufficient to look at experiences during single phases of life, but the whole life history has to be considered.

Since the early 1930s, deep hypothermia (cryoanaesthesia) has been a useful anaesthetic in several types of surgery on neonatal rodents. Especially against the background of modern techniques in systems neuroscience, the method enjoys again increasing popularity. However, little is known about its effects on the subsequent adult behavioural and physiological profile. To systematically investigate the effects of neonatal cryoanaesthesia on adult basal and emotional behaviour as well as on physiological development, 59 C57BL/6 mouse pups were randomly assigned to one of three treatment groups: Pups of the first group were exposed to the hypothermia treatment (H) on postnatal day 3, while pups of the other two groups served as controls: These pups either remained in the home cage without any intervention (C), or were separated from the mother for 15 min (MS) to differentiate between effects of neonatal isolation alone versus hypothermia that inevitably goes along with neonatal isolation. Subsequent behavioural analyses were conducted during adulthood (P 84-P 130), including tests for exploratory, anxiety-like and depression-like behaviour. At the age of about 145 days mice were decapitated to record BDNF levels in the hippocampus and serum corticosterone. Altogether, H mice were found to display slightly increased anxiety levels on the O-Maze, but did not differ from the control animals in any other behavioural test. Subtle alterations in anxiety-like behaviour, however, were not accompanied by physiological changes in serum corticosterone and hippocampal BDNF levels, arguing against an overall long-lasting effect of neonatal hypothermia on the emotional profile of adult mice.

The incidence of major depression is known to be influenced by both genetic and environmental factors. In the current study, we therefore set out to investigate depressive-like behavior and its modification by environmental enrichment using rats bred for 'learned helplessness'. 45 males of congenitally helpless (cLH, n=22) and non-helpless (cNLH, n=23) rats of two different generations were used to systematically investigate differential effects of environmental enrichment on learned helpless behavior, anhedonic-like behavior (sweetened condensed milk consumption) and spontaneous behavior in the home cage. While enrichment was found to reduce learned helpless behavior in 14 weeks old, but not 28 weeks old cLH rats, it did not affect the consumption of sweetened condensed milk. Regarding the home cage behavior, no consistent changes between rats of different strains, housing conditions, and ages were observed. We could thus demonstrate that a genetic predisposition for learned helplessness may interact with environmental conditions in mediating some, but not all depressive-like symptoms in congenitally learned helpless rats. However, future efforts are needed to isolate the differential benefits of environmental factors in mediating the different depression-related symptoms.

Alterations of the glutamatergic system have been implicated in the pathophysiology and treatment of major depression. In order to investigate the expression and function of mGlu5 receptors in an animal model for treatment-resistant depression we used rats bred for congenital learned helplessness (cLH) and the control strain, bred for resistance against inescapable stress, congenitally. not learned helpless rats (cNLH). Western blot analysis showed an increased expression of mGlu5 (but not mGlu1a) receptors in the hippocampus of cLH rats, as compared with control cNLH rats. We also examined mGlu1/5 receptor signaling by in vivo measurement of DHPG-stimulated polyphosphoinositides hydrolysis. Stimulation of 3H-inositolmonophosphate formation induced by i.c.v. injection of DHPG was enhanced by about 50% in the hippocampus of cLH rats. Correspondingly, DHPG-induced long-term depression (LTD) at Schaffer collateral/CA1 pyramidal cell synapses was amplified in hippocampal slices of cLH rats, whereas LTD induced by low frequency stimulation of the Schaffer collaterals did not change. Moreover, these effects were associated with decreased basal dendritic spine density of CA1 pyramidal cell in cLH rats. These data raise the attractive possibility that changes in the expression and function of mGlu5 receptors in the hippocampus might underlie the changes in synaptic plasticity associated with the depressive-like phenotype of cLH rats. However, chronic treatment of cLH rats with MPEP did not reverse learned helplessness, indicating that the enhanced mGlu5 receptor function is not the only player in the behavioral phenotype of this genetic model of depression. This article is part of a Special Issue entitled ‘Metabotropic Glutamate Receptors’.

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.

Investigations of cognitive biases in animals are conceptually and translationally valuable because they contribute to animal welfare research and help to extend and refine our understanding of human emotional disorders, where biased information processing is a critical causal and maintenance factor. We employed the “learned helplessness” genetic rat model of depression in studying cognitive bias and its modification by environmental manipulations. Using a spatial judgment task, responses to ambiguous spatial cues were assessed before and after environmental enrichment to test whether this manipulation would cause an optimistic shift in emotional state. Twenty-four congenitally helpless and nonhelpless male rats were trained to discriminate two different locations, “rewarded” versus “aversive.” After successful acquisition of this spatial discrimination, cognitive bias was probed by measuring responses to three ambiguous locations. Latencies to “reach” and to actively “choose” a goal pot were recorded alongside exploratory behaviors. An overall strain difference was observed, with helpless rats displaying longer “reach” latencies than nonhelpless rats. This implies a “pessimistic” response bias in helpless rats, underscoring their depressive-like phenotype. No strain differences were observed regarding other behavioral measures. Half of the animals were then transferred to enriched cages and retested. Environmental enrichment resulted in reduced “choose” latencies in both rat strains, associating enrichment with more optimistic interpretations of ambiguous cues. Our results emphasize the suitability of cognitive bias measurement for animal emotion assessment. They extend the methodological repertoire for characterizing complex phenotypes and bear implications for animal welfare research and for the use of animal models in preclinical research.

In the past three decades, magnetic resonance imaging (MRI) has been increasingly used in obstetrics to aid diagnostics of maternal and fetal conditions and has generally been considered a safe imaging method. However, the development of higher-performance systems employing, for example, stronger fields to improve the technique's diagnostic potential, necessitates on-going safety evaluation. Rodent studies provide an excellent opportunity to investigate not only acute but also long-term effects of magnetic field exposure in a systematic manner, and a behavioral analysis might help to uncover subtler effects which might result from magnetic field exposure of the vulnerable developing brain. We conducted a comprehensive investigation of emotional and cognitive behavior in adult mice which had been repeatedly exposed to a 7 Tesla static magnetic field in utero. Using well-validated tests, we did not observe any adverse behavioral alterations regarding emotional behavior as well as spatial and emotional learning.

Dopamine plays an important role in learning and memory processes. A deficit of this neurotransmitter as it is apparent in Alzheimer's disease (AD) may contribute to cognitive decline, a major symptom of AD patients. The aim of this study was to elucidate whether or not stimulation of the dopaminergic system leads to an improvement of cognitive function and reduction of non-cognitive behavioral alterations in a murine model of AD. Transgenic and wild type male mice of the TgCRND8 line were treated either with the dopamine precursor levodopa or vehicle and tested in two learning tasks, the object-recognition task and the Barnes maze test. Additionally 24 h spontaneous behavior in the home cage was analyzed. In both memory tasks wild type mice performed significantly better than transgenics. However, transgenics treated with levodopa showed a significant object recognition memory and improved acquisition of spatial memory in the Barnes maze compared to vehicle treated transgenics. Concerning spontaneous behavior transgenic mice performed much more stereotypies than wild types. However, there was a trend for reduced stereotypies in the levodopa group in the time the drug was active. Neurochemical analysis revealed elevated levels of dopamine in the neostriata and frontal cortices and reduced levels in the hippocampi of transgenic mice compared to wild types. Thus cognitive deficits and stereotypies may be due to changes in the dopaminergic system as they could be ameliorated by levodopa treatment, that might also have a therapeutic significance for AD.

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Background Learned helplessness has excellent validity as an animal model for depression, but problems in reproducibility limit its use and the high degree of stress involved in the paradigm raises ethical concerns. We therefore aimed to identify which and how many trials of the learned helplessness paradigm are necessary to distinguish between helpless and non-helpless rats. Findings A trial-by-trial reanalysis of tests from 163 rats with congenital learned helplessness or congenital non-learned helplessness and comparison of 82 rats exposed to inescapable shock with 38 shock-controls revealed that neither the first test trials, when rats showed unspecific hyperlocomotion, nor trials of the last third of the test, when almost all animals responded quickly to the stressor, contributed to sensitivity and specificity of the test. Considering only trials 3–10 improved the classification of helpless and non-helpless rats. Conclusions The refined analysis allows abbreviation of the test for learned helplessness from 15 trials to 10 trials thereby reducing pain and stress of the experimental animals without losing statistical power.