Enriched Housing Research Articles

Environmental enrichment alters locomotor behaviour and ventricular volume in Mecp21lox mice

Rett syndrome (RTT) is an autistic spectrum developmental disorder associated with mutations in the X-linked Mecp2 gene, and severe behavioural and neuropathological deficits. In a mouse model of RTT (Mecp21lox), we examined whether environmental enrichment (EE) alters behavioural performance and regional brain volume. At weaning, Mecp21lox and control mice were assigned to enriched or standard housing. From postnatal day 29 to 43, mice were subjected to behavioural tasks measuring motor and cognitive performance. At postnatal day 44, volumes of whole brain, cerebellum, ventricles, and motor cortex were measured using magnetic resonance imaging. EE provided subtle improvements to locomotor activity and contextual fear conditioning in Mecp21lox mice. Additionally, EE reduced ventricular volumes, which correlated with improved locomotor activity, suggesting that neuroanatomical changes contribute to improved behaviour. Our results suggest that post-weaning EE may provide a non-invasive palliative treatment for RTT.

Effect of environmental enrichment on fearful behavior and gastrin‐releasing peptide receptor expression in the amygdala of prenatal stressed rats

Prenatal stressed offspring exhibit more fearful behavior in behavioral tests, which can be reversed by environmental enrichment (EE). However, the physiological basis of these phenomena remains unclear. Previous studies revealed that abnormal fearful behavior of prenatally stressed offspring may be a consequence of increased activities of CRFergic systems (corticotropin-releasing factor and its receptors) in the amygdala. Gastrin-releasing peptide receptors (GRPR) also have an important role in regulating amygdala-dependent, fear-related learning. The aim of this study was to examine weather prenatal stress and EE can affect the expression of GRPR in the amygdala. We reported here that prenatal chronic stress (subjected to immobilization and bright light stress for 45 min three times per day) caused increased fearfulness in defensive withdrawal test but had no effect on the expression of GRPR in the amygdala. However, enriched environment housing treatment on postnatal days 21-60 can dramatically increase the expression of GRPR in amygdala and reduce fearfulness in the defensive withdrawal test. Our results demonstrate for the first time that EE can modify the expression of GRPR in the amygdala, which might contribute to our understanding of the physiological effects of environmental enrichment.

Sensitivity to reward loss as an indicator of animal emotion and welfare

The scientific study of animal emotion is an important emerging discipline in subjects ranging from neuroscience to animal welfare research. In the absence of direct measures of conscious emotion, indirect behavioural and physiological measures are used. However, these may have significant limitations (e.g. indicating emotional arousal but not valence (positivity versus negativity)). A new approach, taking its impetus from human studies, proposes that biases in information processing, and underlying mechanisms relating to the evaluation of reward gains and losses, may reliably reflect emotional valence in animals. In general, people are more sensitive to reward losses than gains, but people in a negative affective state (e.g. depression) are particularly sensitive to losses. This may underlie broader findings such as an enhanced attention to, and memory of, negative events in depressed individuals. Here we show that rats in unenriched housing, who typically exhibit indicators of poorer welfare and a more negative affective state than those in enriched housing, display a prolonged response to a decrease in anticipated food reward, indicating enhanced sensitivity to reward loss. Sensitivity to reward reduction may thus be a valuable new indicator of animal emotion and welfare.

Nature vs. nurture: Can enrichment rescue the behavioural phenotype of BDNF heterozygous mice?

In earlier experiments we have demonstrated that group-housing in a rather impoverished “standard” environment can be a crucial stress factor in male C57Bl/6 mice. The present study aimed at investigating the effect of combining a probable genetic vulnerability – postulated by the “Neurotrophin Hypothesis of Depression” – with the potentially modulating influence of a stressful environment such as “impoverished” standard housing conditions. For that purpose mice with a partial deletion of brain-derived neurotrophic factor (BDNF) were group-housed under standard and enriched housing conditions and analysed in a well-established test battery for emotional behaviours. Standard group-housing affected emotional behaviour in male and female BDNF heterozygous mice, causing an increase in anxiety, changes in exploration as well as nociception. Providing the animals’ cages with supplementary enrichment, however, led to a rescue of emotional alterations, which emphasises the significance of external factors and their relevance for a valid investigation of genetic aspects in these mutants as well as others, which may be examined in terms of stress-responsiveness or emotionality.

Early enriched housing results in partial recovery of memory deficits in female, but not in male, rats after neonatal hypoxia–ischemia

Our previous results indicated that stimulation by daily environmental enrichment (EE) recovered memory deficits without affecting hippocampus damage in adult male rats submitted to neonatal hypoxia–ischemia (HI). The present study investigated whether early continuous housing in an enriched environment would be effective in preventing spatial and recognition memory both in adolescent and adult female and male rats, as well as the possible benefits of continuous EE in alleviating hippocampal and striatal atrophy consequent to the neonatal HI. Wistar rats in the 7th PND were submitted to the HI and, in the day after, were housed in an enriched environment (8th–30th PND). Subsequently, performance of animals in the novel-object recognition and in two water maze tasks was assessed; in adulthood, animals' behavior was reassessed in the water maze. Rats were sacrificed and both hippocampal volume and striatal area were estimated following the completion of behavioral study. Post-HI cognitive deficits in the object recognition test were completely recovered by the EE. However, memory impairment in the water maze was only partially prevented by EE; this effect was observed especially in female rats on the working memory protocol. As for the morphological assessment, there was no enrichment effect over the loss of hippocampus volume and striatum area. In conclusion, present data indicate that early housing in EE caused performance recovery in object recognition and a partial improvement in the working memory spatial task in adolescent females after neonatal HI; however no effects of enrichment were revealed in adult animal's performance or in the extension of tissue atrophy of hippocampus and striatum consequent to HI.

Effects of environmental enrichment on exploration, anxiety, and memory in female TgCRND8 Alzheimer mice

After we could recently demonstrate a beneficial effect of environmental enrichment on AD-like brain pathology in female TgCRND8 mice [Ambrée O, Leimer U, Herring A, Görtz N, Sachser N, Heneka MT, et al. Reduction of amyloid angiopathy and Abeta plaque burden after enriched housing in TgCRND8 mice: involvement of multiple pathways. Am J Pathol 2006;169:544–52] the present study focuses on the behavioural effects of environmental enrichment with special emphasis on learning and memory performance in this AD model. In the first experiment spontaneous exploration, locomotor activity and anxiety-related behaviour were assessed as the performance in learning tasks can be biased substantially by exploratory behavioural traits. In the second experiment spatial memory in the Barnes maze test and object recognition memory were examined. Regarding exploratory behaviour transgenic mice from standard housing condition were statistically indistinguishable from wild-type controls. Enrichment had comparable effects in both genotypes indicated by higher levels of exploration and locomotor activity. In transgenic mice the elevated plus-maze revealed less anxiety-related behaviour due to enrichment in contrast to wild-type mice that statistically did not differ in anxiety-related behaviour. Concerning learning and memory performance, cognitive deficits of standard housed transgenic mice could be demonstrated in both learning tasks. Surprisingly, in both housing conditions a significantly higher number of transgenic mice refused to explore any objects compared to wild-type mice. Furthermore, the Barnes maze test revealed deficits of the transgenic mice in spatial memory compared to wild-type mice whereas no effect of environmental enrichment was detectable. Thus environmental enrichment increased exploratory behaviour and decreased anxiety-related behaviour but could not clearly ameliorate deficits in learning and memory performance of TgCRND8 mice.

Modulation of dendritic spine remodeling in the motor cortex following spinal cord injury: Effects of environmental enrichment and combinatorial treatment with transplants and neurotrophin‐3

Incomplete spinal cord injury (SCI) elicits structural plasticity of the spared motor system, including the motor cortex, which may underlie some of the spontaneous recovery of motor function seen after injury. Promoting structural plasticity may become an important component of future strategies to improve functional outcomes. We have recently observed dynamic changes in the density and morphology of dendritic spines in the motor cortex following SCI. The present study sought to test whether SCI-induced changes in spine density and morphology could be modulated by potential strategies to enhance functional recovery. We examined the effects of enriched environment, transplants, and neurotrophin-3 on the plasticity of synaptic structures in the motor cortex following SCI. Housing rats in an enriched environment increased spine density in the motor cortex regardless of injury. SCI led to a more slender and elongated spine morphology. Enriched housing mitigated the SCI-induced morphological alterations, suggesting that the environmental modification facilitates maturation of synaptic structures. Transplantation of embryonic spinal cord tissue and delivery of neurotrophin-3 at the injury site further increased spine density when combined with enriched housing. This combinatorial treatment completely abolished the injury-induced changes, restoring a preinjury pattern of spine morphology. These results demonstrated that remodeling of dendritic spines in the motor cortex after SCI can be modulated by enriched housing, and the combinatorial treatment with embryonic transplants and neurotrophin-3 can potentiate the effects of enriched housing. We suggest that synaptic remodeling processes in the motor cortex can be targeted for an intervention to enhance functional recovery after SCI.

Therapeutic effects of complex rearing or bFGF after perinatal frontal lesions

We investigated the effects of an enriched environment and/or basic fibroblast growth factor (bFGF) on recovery from neonatal frontal injury in rats. Rats received medial frontal lesions, or sham surgery, on postnatal day (P) 2/3. In the first set of experiments (Experiments 1 and 2), rats were housed in enriched environments that consisted of a large enclosure with multiple objects (or standard housing) for 90 days beginning at weaning (P22) or in adulthood (P110). In Experiment 3, the rats either received 7 days of subcutaneous bFGF beginning on the day after surgery or bFGF plus enriched housing beginning at weaning. After the 90-day housing period, the animals were tested on a spatial navigation task and a skilled reaching task. Early lesions of the medial frontal cortex caused severe impairments in spatial learning but this deficit was markedly reduced with enriched housing, bFGF, or a combination of both, with the latter being most effective. The housing effects varied with age, however: the earlier the experience began, the better the outcome. Enriched housing increased dendritic length in cortical pyramidal neurons, an effect that was greater in the lesion than the control animals, and enriched housing reversed the lesion-induced decrease in spine density. Enriched environment increased the thickness of the cortical mantle in both lesion and controls whereas bFGF had no effect. Experience thus can affect functional and anatomical outcome after early brain injury but the effects vary with age at experience and may be facilitated by treatment with bFGF.

Towards therapy to relieve memory impairment after anterior thalamic lesions: improved spatial working memory after immediate and delayed postoperative enrichment

Injury to the anterior thalamic nuclei (ATN) is associated with severe amnesia in humans. To test the principle that these deficits may be amenable to intervention, the behavioural effects of postoperative housing in an enriched environment were examined in rats that received neurotoxic lesions of the ATN. As expected, rats with ATN lesions maintained in standard group-housing showed severe, and in this case long-term, deficits in a preoperatively trained non-matching-to-sample spatial working memory task. Thirty days of enriched housing, introduced either at 5 days (Experiment 1) or delayed until 40 days post-surgery (Experiment 2) markedly reduced this working memory impairment, including evidence of improved utilization of spatial cues. The treatment gains found in Experiment 2 were maintained at 4 months post-surgery despite no further enrichment. ATN lesions also retarded the postoperative acquisition of spatial discrimination problems in Experiment 1, irrespective of the separation between target arms, but this impairment was not ameliorated by the prior enrichment. This study provides the first evidence of substantial recovery of severe, and otherwise long-lasting, spatial working memory deficits after ATN brain injury and suggests that further investigation on the extent of possible recovery of function in animal models of diencephalic amnesia is warranted.

Seizure susceptibility and locus ceruleus activation are reduced following environmental enrichment in an animal model of epilepsy

Alterations in the complexity of social and physical housing environments modulate seizure susceptibility in animal models of epilepsy. The studies described here tested the hypothesis that environmental enrichment would delay seizure onset in the epileptic (El) mouse. Neural activation measured via cFos expression, accumulation of the stress neuropeptide corticotropin-releasing factor (CRF), and behavioral seizure susceptibility were quantified in El mice to better understand the mechanisms of ictogenesis. Enrichment housing of El mice from Postnatal Days 21 to 49 produced a 100% decrease in seizure susceptibility relative to El controls. cFos expression increased in the primary motor cortex, locus ceruleus, and hippocampus of El mice relative to ddY controls, an effect attenuated by enrichment housing. CRF levels were elevated by enrichment in the hippocampus of ddY mice only. This study provides evidence that enrichment housing delays the onset of seizure susceptibility in El mice while altering the neuronal and stress-related responses in seizure-associated regions of the El brain.

Effects of environmental enrichment on thermal sensitivity in an operant orofacial pain assay

Environmental enrichment reduces reactivity to stressor and could also modulate pain perception. In this study we sought to compare the effects of enriched and standard housing on temperature perception. In an operant assay, rats housed in an enriched environment exhibited significantly lower sensitivities to thermal stimuli and displayed less exploratory behavior in a rearing chamber. These findings indicate that environmental enrichment can significantly affect temperature perception, likely through stress-related mechanisms.

Life-long environmental enrichment differentially affects the mnemonic response to estrogen in young, middle-aged, and aged female mice

The present study was designed to examine whether life-long exposure to standard or enriched housing affects the ability of estrogen to improve spatial and object memory throughout the lifespan. Three-week-old female mice were maintained in standard or enriched housing up to and through ovariectomy and behavioral testing at 5, 17, or 22 months of age. Spatial memory was tested in the Morris water maze and object memory was tested using an object recognition task. Immediately after training each day, mice were injected intraperitoneally with vehicle or 0.2 mg/kg 17β-estradiol. Among young females, object recognition was enhanced by estradiol alone, an effect that was reduced by enrichment. In contrast, spatial water maze performance was impaired by estradiol alone, but improved by the combination of both estradiol and enrichment. At middle-age, object recognition was enhanced by estradiol or enrichment alone, and the combination of both treatments. Spatial memory in the water maze was also improved by both treatments at middle-age, but the beneficial effects of estradiol were limited to standard-housed females. Finally, whereas enrichment in aged females significantly enhanced performance in both tasks, estradiol had no effect at this age in either task. In total, the data indicate that life-long enrichment can significantly alter the extent to which estradiol affects memory in mice throughout the lifespan. Importantly, the interaction between these treatments is highly dependent on age and type of memory tested.

Animal welfare in organic farming systems

AbstractThe concept of farm animal welfare can, for practical purposes, be translated into the so‐called Five Freedoms.1 Organic farming aims to meet animal welfare needs and should therefore comply with these Freedoms. The first Freedom, from hunger and thirst, is met in any system properly managed to organic standards. The Freedom from thermal and physical discomfort is challenged as organic husbandry systems face more climatic extremes. However, they also provide more ‘control’ to the animal by offering a choice when seeking warmth or a cool place to lie. The Freedom from pain, injury and disease is the most complicated one. Organic farming virtually bans mutilations (e.g. debeaking, tail docking), although some are still allowed and practised (e.g. castration). Organic animals are more exposed to wildlife and at risk of contracting infectious diseases. However, it is possible (although not proven) that organically managed animals are more resistant to illness. The Freedom to express normal behaviour is met through environmental enrichment and group housing. The Freedom from fear and distress is supported by e.g. extra (social) space. In conclusion, if animal health can be maintained, organic farming is very well placed to provide good animal welfare. Copyright © 2007 Society of Chemical Industry

Age-dependent effects of environmental enrichment on spatial reference memory in male mice

Although environmental enrichment has been shown to improve various types of memory in young and aging mice, no study has directly compared the degree to which enrichment improves memory at different ages throughout the lifespan in male mice. Therefore, the present study investigated the effects of long-term continuous enrichment in young (3 months), middle-aged (15 months), and aged (21 months) male C57BL/6 mice. Spatial reference memory was tested in the Morris water maze. Results demonstrate that 24 h/day environmental enrichment for approximately 6 weeks significantly improved spatial memory in the Morris water maze in aged males, but not in young or middle-aged males. These data also indicate that 24 h exposure to complex enriched housing conditions increases the magnitude of enrichment-induced improvements in memory among aged mice relative to those previously reported by this lab and others.

Short-term environmental enrichment decreases the mnemonic response to estrogen in young, but not aged, female mice

The present study was designed to examine if 4 weeks of exposure to an enriched housing environment affects the ability of estrogen to facilitate object recognition in young and aged female mice. Object recognition was tested using a novel object recognition task. Ovariectomized young and aged female mice were maintained in standard or enriched housing for 4 weeks prior to and then throughout object recognition testing. Immediately after training, mice were injected intraperitoneally with vehicle or 0.2 mg/kg 17 β-estradiol and then were re-tested 24 and 48 h later. Among young females, estradiol alone improved object recognition at both delays relative to chance, an effect not present in enriched females treated with estradiol. Enrichment alone had no significant effect on object recognition in young females at either delay. In contrast, enrichment alone in aged females significantly enhanced both 24- and 48-h object recognition relative to chance, an effect not present in mice treated with both enrichment and estradiol. Estradiol alone had no effect on object recognition in aged females at either delay. Together, these data indicate that estradiol and enrichment alone differentially affect object recognition in young and aged females. However, the fact that the combination of estradiol and enrichment treatments did not affect object recognition at either age suggests that co-administration of both treatments is less effective than the most effective single treatment at each age.

The behavioral effects of enriched housing are not altered by serotonin depletion but enrichment alters hippocampal neurochemistry

To assess a possible role for serotonin in the mediation of the behavioral changes induced by enriched housing conditions (EC), adult female Long–Evans rats sustaining a serotonin depletion (150 μg of 5,7-dihydroxytryptamine, icv) and sham-operated rats were housed postoperatively for 30 days in enriched (12 rats/large cage containing various objects) or standard housing conditions (2 rats/standard laboratory cage). Thereafter, anxiety responses (elevated plus-maze), locomotor activity (in the home-cage), sensori-motor capabilities (beam-walking task), and spatial memory (eight-arm radial maze) were assessed. Monoamine levels were subsequently measured in the frontoparietal cortex and the hippocampus. Overall, EC reduced anxiety-related responses, enhanced sensori-motor performance and improved the memory span in the initial stage of the spatial memory task. Despite a substantial reduction of serotonergic markers in the hippocampus (82%) and the cortex (74%), these positive effects of EC were not altered by the lesion. EC reduced the serotonin levels in the ventral hippocampus (particularly in unlesioned rats: −23%), increased serotonin turnover in the entire hippocampus (particularly in lesioned rats: +36%) and augmented the norepinephrine levels in the dorsal hippocampus (+68% in unlesioned and +49% in lesioned rats); no such alterations were found in the frontoparietal cortex. Our data suggest that an intact serotonergic system is not a prerequisite for the induction of positive behavioral effects by EC. The neurochemical changes found in the hippocampus of EC rats, however, show that the monoaminergic innervation of the hippocampus is a target of EC.

Influence of Aging and Enriched Environment on Motor Activity and Emotional Responses in Mice

We have evaluated different behavioral parameters in ICR (CD1) female mice of three different ages (38-39 weeks: mature; 62 weeks: late mature; 90 weeks: old), and addressed the effects of an enriched housing condition. We employed the following battery of tests: Holeboard, open field, elevated plus-maze (EPM), and forced swimming test (FST). The results suggest that aging process differentially affects diverse aspects of behavior. With respect to motor activity, late mature animals were more affected by enrichment, whereas old animals appeared to be more affected when emotional responses were considered. We propose that the diminished percentage of time in the open arms of the EPM showed by enriched mice may be indicative of decreased novelty seeking, whereas their decreased climbing behavior may indicate a reduced escape-related behavior in an inescapable situation.

Preweaning housing effects on behavior and physiological measures in pigs during the suckling and fattening periods1

The effect of the preweaning housing system on the stress response of pigs before weaning and during fattening was studied in 33 litters of domestic pigs. Three preweaning housing systems were compared: barren crate (standard farrowing crate without straw), enriched crate (20% larger crate, with straw), and as a control, a farrowing pen (pen, 60% larger than the barren crate, with straw). At 25 d of age, pigs were tested with an isolation test and 1 d later with a human approach test (HumanT). Pigs were weaned at 28 d of age. At 3 and 6 mo of age, pigs were tested with an isolation-human approach test. The latency and frequency of squeal calls and locomotor activity were analyzed for all 3 tests, whereas physical contact with the human was also analyzed for the HumanT and isolation-human approach test. At 6 mo of age, the pigs were transported to a slaughterhouse. One day before transport, immediately after transport, and 1 h after transport, saliva samples were taken for cortisol analysis. The pH of the LM was also measured 45 min after slaughter. Preweaning housing system affected (P < 0.05) the probability of squeal vocalizations, the latency of locomotion, and the duration of locomotion during the HumanT. Pigs from the enriched pens vocalized less, had a longer latency to move, and performed less overall locomotion than pigs from the barren crates. Preweaning housing system did not affect behavior of fattening pigs. Cortisol concentrations before and after transport were not affected by preweaning housing system. An interaction of cortisol concentrations and housing systems was observed between the control sample and the sample taken immediately after transport in pigs from the barren crates (P < 0.05) compared with pigs from the enriched housing systems. Meat from pigs reared in the barren crate tended to have lower pH (P < 0.10) and that of pigs reared in enriched crates had lower pH (P < 0.05) than meat of pigs reared in enriched pens. No differences were observed between pigs from barren or enriched crates. Our results suggest that enrichment of the preweaning environment through enlarged space, provision of straw, and free movement for the sow had a positive effect on the coping behavior of pigs before weaning and prevented an increase in salivary cortisol concentration immediately after transport and a decrease in meat pH 45 min postmortem at the age of 6 mo. Minimal enrichment of the commercial farrowing crate did not affect behavior and physiological measures in pigs before and after weaning.

Enriched environment enhances transplanted subventricular zone stem cell migration and functional recovery after stroke

Stroke patients suffer from severe impairments and significant effort is under way to develop therapies to improve functional recovery. Stem cells provide a promising form of therapy to replace neuronal circuits lost to injury. Indeed, previous studies have shown that a variety of stem cell types can provide some functional recovery in animal models of stroke. However, it is unlikely that replacement therapy alone will be sufficient to maximize recovery. The aim of the present study was to determine if rodent stem cell transplants combined with rehabilitation resulted in enhanced functional recovery after focal ischemia in rats. Middle cerebral artery occlusion was induced by injection of the vasoconstrictive peptide endothelin-1 adjacent to the middle cerebral artery. Seven days after stroke the rats received adult neural stem cell transplants isolated from mouse subventricular zone or vehicle injection and then subsequently were housed in enriched or standard conditions. The rats in the enriched housing also had access to running wheels once a week. Enriched housing and voluntary running exercise enhanced migration of transplanted stem cells toward the region of injury after stroke and there was a trend toward increased survival of stem cells. Enrichment also increased the number of endogenous progenitor cells in the subventricular zone of transplanted animals. Finally, functional recovery measured in the cylinder test was facilitated only when the stem cell transplants were combined with enrichment and running exercise 7 days after the transplant. These results suggest that the ability of transplanted stem cells in promoting recovery can be augmented by environmental factors such as rehabilitation.

Enriched environment promotes adult neural progenitor cell mobilization in mouse demyelination models

Since the discovery of adult neural stem cells, mobilization of endogenous stem cells from the subventricular zone (SVZ) emerges as a promising strategy to promote brain repair. Here, we examined the effect of environment enrichment on SVZ cell mobilization in demyelinating pathologies. We showed that enriched housing conditions reduced functional impairment in experimental autoimmune encephalomyelitis (EAE), a rodent model of multiple sclerosis. Furthermore, both in a focal demyelination model (lysolecithin injection) and in the inflammatory EAE model, SVZ mitotic activity and the number of SVZ-derived cells in demyelinated areas were significantly increased by environment enrichment. Enriched housing conditions also promoted the oligodendrocyte fate of SVZ-recruited cells in the EAE lesions. Altogether our results show that environment enrichment provides beneficial conditions to promote the mobilization of neural progenitors into demyelinating lesions and to favour functional recovery.