Home Cage Environment Research Articles

Social isolation is closely linked to a marked reduction in physical activity in male mice

The effects of social isolation on an individual's behavior is an important field of research, especially as public health officials encourage social distancing to prevent the spread of pandemic disease. In this study we evaluate the effects of social isolation on physical activity in mice. Utilizing a pixel-based tracking system, we continuously monitored the movement of isolated mice compared with paired cage mates in the home cage environment. We demonstrate that mice that are socially isolated dramatically decrease their movement when separated from their cage mate, and especially in the dark cycle, when mice are normally most active. When isolated mice are re-paired with their original cage mate, this effect is reversed, and mice return to their prior levels of activity. These findings suggest a close link between social isolation and physical activity, and are of particular interest in the wake of coronavirus disease 2019, when many are forced into isolation. Social isolation may affect an individual's overall activity levels in humans too, which may have unintended effects on health that deserve further consideration.

An automated homecage system for multiwhisker detection and discrimination learning in mice.

Automated, homecage behavioral training for rodents has many advantages: it is low stress, requires little interaction with the experimenter, and can be easily manipulated to adapt to different experimental conditions. We have developed an inexpensive, Arduino-based, homecage training apparatus for sensory association training in freely-moving mice using multiwhisker air current stimulation coupled to a water reward. Animals learn this task readily, within 1–2 days of training, and performance progressively improves with training. We examined the parameters that regulate task acquisition using different stimulus intensities, directions, and reward valence. Learning was assessed by comparing anticipatory licking for the stimulus compared to the no-stimulus (blank) trials. At high stimulus intensities (>9 psi), animals showed markedly less participation in the task. Conversely, very weak air current intensities (1–2 psi) were not sufficient to generate rapid learning behavior. At intermediate stimulus intensities (5–6 psi), a majority of mice learned that the multiwhisker stimulus predicted the water reward after 24–48 hrs of training. Both exposure to isoflurane and lack of whiskers decreased animals’ ability to learn the task. Following training at an intermediate stimulus intensity, mice were able to transfer learning behavior when exposed to a lower stimulus intensity, an indicator of perceptual learning. Mice learned to discriminate between two directions of stimulation rapidly and accurately, even when the angular distance between the stimuli was <15 degrees. Switching the reward to a more desirable reward, aspartame, had little effect on learning trajectory. Our results show that a tactile association task in an automated homecage environment can be monitored by anticipatory licking to reveal rapid and progressive behavioral change. These Arduino-based, automated mouse cages enable high-throughput training that facilitate analysis of large numbers of genetically modified mice with targeted manipulations of neural activity.

Cage-lid hanging behavior as a translationally relevant measure of pain in mice.

The development of new analgesic drugs has been hampered by the inability to translate preclinical findings to humans. This failure is due in part to the weak connection between commonly used pain outcome measures in rodents and the clinical symptoms of chronic pain. Most rodent studies rely on the use of experimenter-evoked measures of pain and assess behavior under ethologically unnatural conditions, which limits the translational potential of preclinical research. Here, we addressed this problem by conducting an unbiased, prospective study of behavioral changes in mice within a natural homecage environment using conventional preclinical pain assays. Unexpectedly, we observed that cage-lid hanging, a species-specific elective behavior, was the only homecage behavior reliably impacted by pain assays. Noxious stimuli reduced hanging behavior in an intensity-dependent manner, and the reduction in hanging could be restored by analgesics. Finally, we developed an automated approach to assess hanging behavior. Collectively, our results indicate that the depression of hanging behavior is a novel, ethologically valid, and translationally relevant pain outcome measure in mice that could facilitate the study of pain and analgesic development.

Examining changes in rodent temperament following repetitive mild traumatic brain injury in adolescence.

Mild traumatic brain injuries are known to cause a host of symptoms, including headaches, nausea, and depression, that when persistent, are known as postconcussive syndrome. In addition to these overt symptomologies, individuals may experience changes in day-to-day behavior or temperament, which although not meeting criteria for postconcussive diagnosis, does cause distress to the individual. The aim of this study was to determine whether we could measure temperament in a rat and, if so, determine whether temperament is altered in response to repetitive mild traumatic brain injuries (RmTBI). Forty male and female adolescent Sprague-Dawley rats were same-sex pair housed and subjected to RmTBIs or sham injuries. The rats were recorded at 6 different time points throughout the study for the temperament assessment protocol, a measure of the complex behavioral profile of each rat within its dyadic home cage environment. The temperaments were quantified via a novel behavioral scoring algorithm. The rats were also tested on a battery of tests that were designed to measure symptoms of postconcussion syndrome. We determined that rodent temperament is quantifiable, is sex dependent, changes with age, and is modifiable in response to experiential factors such as RmTBI. Rats that received the RmTBIs were significantly less active and showed decreased levels of social interaction compared with their sham-injury counterparts. Moreover, both task switching and recovery patterns for RmTBI rats were dependent on the injury status of their cage mates. Future studies are now required to determine the mechanisms underlying these important changes in temperament. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Drug-responsive autism phenotypes in the 16p11.2 deletion mouse model: a central role for gene-environment interactions

There are no current treatments for autism, despite its high prevalence. Deletions of chromosome 16p11.2 dramatically increase risk for autism, suggesting that mice with an equivalent genetic rearrangement may offer a valuable model for the testing of novel classes of therapeutic drug. 16p11.2 deletion (16p11.2 DEL) mice and wild-type controls were assessed using an ethological approach, with 24 h monitoring of activity and social interaction of groups of mice in a home-cage environment. The ability of the excitation/inhibition modulator N-acetyl cysteine (NAC) and the 5-HT1B/1D/1F receptor agonist eletriptan to normalise the behavioural deficits observed was tested. 16p11.2 DEL mice exhibited largely normal behaviours, but, following the stress of an injection, showed hyperlocomotion, reduced sociability, and a strong anxiolytic phenotype. The hyperactivity and reduced sociability, but not the suppressed anxiety, were effectively attenuated by both NAC and eletriptan. The data suggest that 16p11.2 DEL mice show an autism-relevant phenotype that becomes overt after an acute stressor, emphasising the importance of gene-environmental interactions in phenotypic analysis. Further, they add to an emerging view that NAC, or 5-HT1B/1D/1F receptor agonist treatment, may be a promising strategy for further investigation as a future treatment.

Longitudinal changes in EEG power, sleep cycles and behaviour in a tau model of neurodegeneration

BackgroundDisturbed sleep is associated with cognitive decline in neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The progressive sequence of how neurodegeneration affects aspects of sleep architecture in conjunction with behavioural changes is not well understood.MethodsWe investigated changes in sleep architecture, spectral power and circadian rhythmicity in the tet-off rTg4510 mouse overexpressing human P301L tau within the same subjects over time. Doxycycline-induced transgene-suppressed rTg4510 mice, tTa carriers and wild-type mice were used as comparators. Spectral power and sleep stages were measured from within the home cage environment using EEG electrodes. In addition, locomotor activity and performance during a T-maze task were measured.ResultsSpectral power in the delta and theta bands showed a time-dependent decrease in rTg4510 mice compared to all other groups. After the initial changes in spectral power, wake during the dark period increased whereas NREM and number of REM sleep bouts decreased in rTg4510 compared to wild-type mice. Home cage locomotor activity in the dark phase significantly increased in rTg4510 compared to wild-type mice by 40 weeks of age. Peak-to-peak circadian rhythm amplitude and performance in the T-maze was impaired throughout the experiment independent of time. At 46 weeks, rTG4510 mice had significant degeneration in the hippocampus and cortex whereas doxycycline-treated rTG4510 mice were protected. Pathology significantly correlated with sleep and EEG outcomes, in addition to locomotor and cognitive measures.ConclusionsWe show that reduced EEG spectral power precedes reductions in sleep and home cage locomotor activity in a mouse model of tauopathy. The data shows increasing mutant tau changes sleep architecture, EEG properties, behaviour and cognition, which suggest tau-related effects on sleep architecture in patients with neurodegenerative diseases.

Automated Analysis of Stroke Mouse Trajectory Data With Traja.

Quantitative characterization of mouse activity, locomotion and walking patterns requires the monitoring of position and activity over long periods of time. Manual behavioral phenotyping, however, is time and skill-intensive, vulnerable to researcher bias and often stressful for the animals. We present examples for using a platform-independent open source trajectory analysis software, Traja, for semi-automated analysis of high throughput mouse home-cage data for neurobehavioral research. Our software quantifies numerous parameters of movement including traveled distance, velocity, turnings, and laterality which are demonstrated for application to neurobehavioral analysis. In this study, the open source software for trajectory analysis Traja is applied to movement and walking pattern observations of transient stroke induced female C57BL/6 mice (30 min middle cerebral artery occlusion) on an acute multinutrient diet intervention (Fortasyn). After stroke induction mice were single housed in Digital Ventilated Cages [DVC, GM500, Tecniplast S.p.A., Buguggiate (VA), Italy] and activity was recorded 24/7, every 250 ms using a DVC board. Significant changes in activity, velocity, and distance walked are computed with Traja. Traja identified increased walked distance and velocity in Control and Fortasyn animals over time. No diet effect was found in preference of turning direction (laterality) and distance traveled. As open source software for trajectory analysis, Traja supports independent development and validation of numerical methods and provides a useful tool for computational analysis of 24/7 mouse locomotion in home-cage environment for application in behavioral research or movement disorders.

Low-cost solution for rodent home-cage behaviour monitoring.

In the current research on measuring complex behaviours/phenotyping in rodents, most of the experimental design requires the experimenter to remove the animal from its home-cage environment and place it in an unfamiliar apparatus (novel environment). This interaction may influence behaviour, general well-being, and the metabolism of the animal, affecting the phenotypic outcome even if the data collection method is automated. Most of the commercially available solutions for home-cage monitoring are expensive and usually lack the flexibility to be incorporated with existing home-cages. Here we present a low-cost solution for monitoring home-cage behaviour of rodents that can be easily incorporated to practically any available rodent home-cage. To demonstrate the use of our system, we reliably predict the sleep/wake state of mice in their home-cage using only video. We validate these results using hippocampal local field potential (LFP) and electromyography (EMG) data. Our approach provides a low-cost flexible methodology for high-throughput studies of sleep, circadian rhythm and rodent behaviour with minimal experimenter interference.

Effects of haloperidol on cognitive function and behavioural flexibility in the IntelliCage social home cage environment

This study examined the effects of chronic administration of haloperidol in female C57BL/6 mice. As patients with schizophrenia often show perseverant behaviours and lack of behavioural flexibility, it is important to know whether the effect of haloperidol makes these traits worse. This study, therefore, was designed to evaluate the effects of haloperidol on the learning performance of mice using an automated home cage environment, the IntelliCage. Behavioural shuttling in the IntelliCage enabled us to assess learning in tasks including place discrimination learning and reversal place learning. In reversal place learning, spatial patterns of rewarded and non-rewarded places that mice had learned to discriminate were reversed, and the adaptability of mice to change the previously acquired place learning was measured. Haloperidol (1 mg/kg/day) reduced locomotor activity and water intake. Haloperidol impaired the cognitive flexibility of mice during reversal place learning rewarded by access to water but enhanced the rapid acquisition of behavioural flexibility when airpuff punishment was applied.

Postweaning Isolation Rearing Alters the Adult Social, Sexual Preference and Mating Behaviors of Male CD-1 Mice.

Objective: No study has comprehensively evaluated the effect of postweaning isolation on the social and sexual behaviors of a certain strain of rodents in ethology. The present study aims to explore how and to what extent isolation rearing after postweaning affects the social and sexual behaviors of male CD-1 mice in adulthood systematically.Methods: Male CD-1 mice were randomly assigned to two groups: isolation reared (IS, one mouse per cage, n = 30) and group housed (GH, five mice per cage, n = 15). The mice underwent isolation rearing from postnatal day 23 to day 93. Then, social affiliation, recognition and memory were measured through selection task experiments. Social interaction under a home cage and novel environment were measured via resident–intruder and social interaction test, respectively. Furthermore, sexual preference, homosexual and heterosexual behaviors were measured.Results: Our study found that postweaning isolation increased the social affiliation for conspecifics (p = 0.001), reduced social recognition (p = 0.042) and impaired social memory. As for social interaction, isolated mice showed a remarkably increased aggression toward the intruder male in a home cage or novelty environment. For instance, isolated mice presented a short attack latency (p < 0.001), high attack frequency (p < 0.001) and long attack duration (p < 0.001). In addition, isolated mice exhibited further social avoidance. Contrastingly, isolated mice displayed a reduced sexual preference for female (IS: 61.47 ± 13.80%, GH: 70.33 ± 10.06%, p = 0.038). As for heterosexual behavior, isolated mice have a short mating duration (p = 0.002), long mounting latency (p = 0.002), and long intromission latency (p = 0.015). However, no association was observed between postweaning isolation and homosexual behavior in male CD-1 mouse.Conclusion: Postweaning isolation increased the social affiliation, impaired the social cognition and considerably increased the aggression in social interaction of adult male CD-1 mice. Postweaning isolation induced a decreased sexual preference for female in adulthood. Postweaning isolation extended the latency to mate, thereby reducing mating behavior. No association was observed between isolation and homosexual behavior.

Mouse incising central pattern generator: Characteristics and modulation by pain

IntroductionVertebrate incising and chewing are controlled by a set of neurons comprising the central pattern generator (CPG) for mastication. Mandibular positioning and force generation to perform these tasks is complex and requires coordination of multiple jaw opening and closing muscle compartments located in muscles on both sides of the jaw. The purpose of this study was to determine the characteristics of the CPG by recording mouse incising forces in the home cage environment to evaluate changes in force characteristics with incising frequency and force direction. A second purpose was to evaluate the effects of jaw closing muscle pain on CPG output parameters. MethodsDigitized incising forces were recorded for approximately 24 h using a 3-dimensional force transducer attached to solid food chow. Male and female CD-1 mice were evaluated during their last (fourth) baseline assessment and seven days after a second acidic saline injection into the left masseter muscle when maximum pain was experienced. Incising force resultants were calculated from the three axes data and force parameters were assessed including inter-peak intervals (IPI), peak amplitude, load time and unload time. Multiple regression analyses were conducted to identify incising episodes that had parameters of force that were significantly correlated (p < 0.001). These incising episodes were considered to represent the output of the CPG with a steady state of incoming sensory afferent inputs. Incising parameters were evaluated for each of the discrete incising frequencies (4.6, 5.3, 6.2, 7.6 Hz) and the predominant force directions: jaw closing (−Z), jaw retrusion (+X) and jaw protrusion (−X). ResultsA significant correlation between incising frequency (IPI) and the load time was observed. A significant decrease in peak amplitude was observed with higher incising frequency while the load rate significantly increased. The force peak amplitude and load rates were found to be statistically different when the force direction was considered, with smaller peak amplitudes and smaller load rates found in the jaw closing direction. The effect of pain on incising was to reduce the peak amplitude and load rate of incising compared to the baseline condition at lower incising frequencies. ConclusionsLike the central pattern generator for locomotion, the CPG for incising controls rhythmicity, peak amplitude and force load duration/rate. However, unlike the CPG for locomotion, the amplitude of incising force decreases as the frequency increases. During incising, load rate increases with faster rhythm and is consistent with the recruitment of larger motor units. Muscle pain reduced the excitatory drive of the CPG on motoneurons and provides further support of the Pain Adaptation Model.

Involvement of Serotonergic and Relaxin-3 Neuropeptide Systems in the Expression of Anxiety-like Behavior

Anxiety-related defensive behavior is controlled by a distributed network of brain regions and interconnected neural circuits. The dorsal raphe nucleus (DR), which contains the majority of forebrain-projecting serotonergic neurons, is a key brain region involved in fear states and anxiety-related behavior via modulation of this broad neural network. Evidence suggests that relaxin-3 neurons in the nucleus incertus (NI) may also interact with this network, however, the potential role of the NI in the control of anxiety-related defensive behavior requires further investigation. In this study, we examined the response of an anxiety-related neuronal network, including serotonergic neurons in the DR and relaxin-3-containing neurons in the NI, to administration of an anxiogenic drug and exposure to an aversive environment. We administered an anxiogenic dose of the adenosine receptor antagonist, caffeine (50 mg/kg, i.p.), or vehicle, to adult male Wistar rats and 30 min later exposed them to either an elevated plus-maze (EPM) or a home cage environment. Administration of caffeine and exposure to the EPM activated a broad network of brain regions involved in control of anxiety-like behaviors, including serotonergic neurons in the DR, as measured using c-Fos immunohistochemistry. However, only exposure to the EPM activated relaxin-3-containing neurons in the NI, and activation of these neurons was not correlated with changes in anxiety-like behavior. These data suggest activation of the NI relaxin-3 system is associated with expression of behavior in tests of anxiety, but may not be directly involved in the approach-avoidance conflict inherent in anxiety-related defensive behavior in rodents.

Shock-probe Defensive Burying Test to Measure Active versus Passive Coping Style in Response to an Aversive Stimulus in Rats

Maladaptive avoidance behaviors are seen in many stress-related psychiatric illnesses. Patients with these illnesses favor passive, avoidant coping strategies rather than adaptive, active coping strategies. Preclinically, coping strategy can be measured in rats using the shock-probe defensive burying test, wherein rats receive a shock from an electrified probe inserted into a test cage that mimics their home cage environment, and behavioral output (immobility or burying) is recorded for 15 min following the shock. Immobility in response to the perceived threat of the shock-probe, associated with elevated stress hormone levels, is regarded as a passive, maladaptive coping strategy. In opposition, burying the probe is associated with lower stress hormone levels and is considered an active, adaptive coping style. In rats, chronic stress induces a shift from active to passive coping in this test (i.e., proportionally less burying and more immobility), modeling the avoidant symptoms presented across many stress-related psychiatric illnesses. The stress-induced shifts in coping style and overall behavioral reactivity to the shock-probe provide a unique and well-validated measure of not only an anxiety-like behavioral response but also coping strategy selection in rat models of psychiatric illness.

The BACHD Rat Model of Huntington Disease Shows Specific Deficits in a Test Battery of Motor Function.

Rationale: Huntington disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive and neuropsychiatric symptoms. HD is usually diagnosed by the appearance of motor deficits, resulting in skilled hand use disruption, gait abnormality, muscle wasting and choreatic movements. The BACHD transgenic rat model for HD represents a well-established transgenic rodent model of HD, offering the prospect of an in-depth characterization of the motor phenotype.Objective: The present study aims to characterize different aspects of motor function in BACHD rats, combining classical paradigms with novel high-throughput behavioral phenotyping.Methods: Wild-type (WT) and transgenic animals were tested longitudinally from 2 to 12 months of age. To measure fine motor control, rats were challenged with the pasta handling test and the pellet reaching test. To evaluate gross motor function, animals were assessed by using the holding bar and the grip strength tests. Spontaneous locomotor activity and circadian rhythmicity were assessed in an automated home-cage environment, namely the PhenoTyper. We then integrated existing classical methodologies to test motor function with automated home-cage assessment of motor performance.Results: BACHD rats showed strong impairment in muscle endurance at 2 months of age. Altered circadian rhythmicity and locomotor activity were observed in transgenic animals. On the other hand, reaching behavior, forepaw dexterity and muscle strength were unaffected.Conclusions: The BACHD rat model exhibits certain features of HD patients, like muscle weakness and changes in circadian behavior. We have observed modest but clear-cut deficits in distinct motor phenotypes, thus confirming the validity of this transgenic rat model for treatment and drug discovery purposes.

Automated recording of home cage activity and temperature of individual rats housed in social groups: The Rodent Big Brother project.

Measuring the activity and temperature of rats is commonly required in biomedical research. Conventional approaches necessitate single housing, which affects their behavior and wellbeing. We have used a subcutaneous radiofrequency identification (RFID) transponder to measure ambulatory activity and temperature of individual rats when group-housed in conventional, rack-mounted home cages. The transponder location and temperature is detected by a matrix of antennae in a baseplate under the cage. An infrared high-definition camera acquires side-view video of the cage and also enables automated detection of vertical activity. Validation studies showed that baseplate-derived ambulatory activity correlated well with manual tracking and with side-view whole-cage video pixel movement. This technology enables individual behavioral and temperature data to be acquired continuously from group-housed rats in their familiar, home cage environment. We demonstrate its ability to reliably detect naturally occurring behavioral effects, extending beyond the capabilities of routine observational tests and conventional monitoring equipment. It has numerous potential applications including safety pharmacology, toxicology, circadian biology, disease models and drug discovery.

Food Seeking in a Risky Environment: A Method for Evaluating Risk and Reward Value in Food Seeking and Consumption in Mice.

Most studies that measure food intake in mice do so in the home cage environment. This necessarily means that mice do not engage in food seeking before consumption, a behavior that is ubiquitous in free-living animals. We modified and validated several commonly used anxiety tests to include a palatable food reward within the anxiogenic zone. This allowed us to assess risk-taking behavior in food seeking in mice in response to different metabolic stimuli. We modified the open field test and the light/dark box by placing palatable peanut butter chips within a designated food zone inside the anxiogenic zone of each apparatus. We then assessed parameters of the interaction with the food reward. Fasted mice or mice treated with ghrelin showed increased consumption and increased time spent in the food zone immediately around the food reward compared to ad libitum fed mice or mice treated with saline. However, fasted mice treated with IP glucose before exposure to the behavioral arena showed reduced time in the food zone compared to fasted controls, indicating that acute metabolic signals can modify the assessment of safety in food seeking in a risky environment. The tests described in this study will be useful in assessing risk processing and incentive salience of food reward, which are intrinsic components of food acquisition outside of the laboratory environment, in a range of genetic and pharmacological models.

Creatine transporter deficiency leads to increased whole body and cellular metabolism.

Creatine (Cr) is a guanidino compound required for rapid replenishment of ATP in cells with a high-energy demand. In humans, mutations in the Cr transporter (CRT;SLC6A8) prevent Cr entry into tissue and result in a significant intellectual impairment, epilepsy, and aphasia. The lack of Cr on both the whole body and cellular metabolism was evaluated in Crt knockout (Crt (-/y) ) mice, a high-fidelity model of human CRT deficiency. Crt (-/y) mice have reduced body mass and, however, show a twofold increase in body fat. There was increased energy expenditure in a home cage environment and during treadmill running in Crt (-/y) mice. Consistent with the increases in the whole-body metabolic function, Crt (-/y) mice show increased cellular metabolism as well. Mitochondrial respiration increased in skeletal muscle fibers and hippocampal lysates from Crt (-/y) mice. In addition, Crt (-/y) mice had increased citrate synthase activity, suggesting a higher number of mitochondria instead of an increase in mitochondrial activity. To determine if the increase in respiration was due to increased mitochondrial numbers, we measured oxygen consumption in an equal number of mitochondria from Crt (+/y) and Crt (-/y) mice. There were no changes in mitochondrial respiration when normalized to mitochondrial number, suggesting that the increase in respiration observed could be to higher mitochondrial content in Crt (-/y) mice.

Analysis of Individual Mouse Activity in Group Housed Animals of Different Inbred Strains using a Novel Automated Home Cage Analysis System.

Central nervous system disorders such as autism as well as the range of neurodegenerative diseases such as Huntington's disease are commonly investigated using genetically altered mouse models. The current system for characterizing these mice usually involves removing the animals from their home-cage environment and placing them into novel environments where they undergo a battery of tests measuring a range of behavioral and physical phenotypes. These tests are often only conducted for short periods of times in social isolation. However, human manifestations of such disorders are often characterized by multiple phenotypes, presented over long periods of time and leading to significant social impacts. Here, we have developed a system which will allow the automated monitoring of individual mice housed socially in the cage they are reared and housed in, within established social groups and over long periods of time. We demonstrate that the system accurately reports individual locomotor behavior within the group and that the measurements taken can provide unique insights into the effects of genetic background on individual and group behavior not previously recognized.

Developmental and behavioral consequences of early life maternal separation stress in a mouse model of fetal alcohol spectrum disorder

Prenatal alcohol exposure (PAE) can result in fetal alcohol spectrum disorder (FASD), characterized by developmental disability. As children with FASD are often raised in suboptimal conditions, we have investigated the combination of PAE via maternal preference consumption of 10% ethanol in water with early life stress (ELS) via daily 3h maternal separation and isolation. Our results focus on development and behavioral features, including activity, anxiety-like behavior, as well as learning and memory. PAE influenced the number of pups surviving to postnatal day 2 and 70, with fewer surviving pups associated with the severity of ethanol exposure. PAE and ELS both had effects on pup weight at postnatal day 21, with amount of ethanol exposure positively correlating with pup weight. We found females were more active than males in a novel open field environment, but not following PAE. In addition, PAE resulted in overall increased exploratory behavior in the open field. Further, PAE and ELS both resulted in overnight hypoactivity in a home cage environment, as well as learning deficits that were influenced by sex in the Barnes Maze for learning and memory. These results are attributed to environmental interactions involving PAE and ELS.

Play matters: the surprising relationship between juvenile playfulness and anxiety in later life

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.