Environmental Enrichment – Positive Challenge
Environmental enrichment (EE), classically defined as "a combination of complex inanimate and social stimulation", has long been used to investigate the influence of environment on brain and behavior. Typically, the EE paradigm consist of housing animals in large groups, in relatively spacious and complex cages, with a variety of objects (e.g. nesting material, running wheels, and tunnels) that facilitate enhanced sensory, cognitive, motor, and social stimulation relative to standard laboratory housing conditions. Most important, an enriched environment provides the animals with opportunities to perform some of their species-specific behavioral repertoire. Since the pioneer experiments by Rosenzweig and colleagues, which introduced EE as an experimental protocol, many studies have demonstrated that environmental stimulation elicits a variety of positive effects on the brain at the molecular, anatomical and behavioral levels. Exposure to EE increases hippocampal neurogenesis, enhances learning and memory, and induces neural plasticity. EE has robust beneficial effects on animal models of neurodegenerative diseases, such as Huntington’s disease, Alzheimer’s disease, and Parkinson’s disease, and psychiatric disorders such as schizophrenia and drug addiction. In addition, several studies have demonstrated that EE attenuates stress and anxiety-like responses evoked by psychogenic and neurogenic stressors, thus exerting a therapeutic and protective (anxiolytic) effect.
Summary of selected projects:
1. The anxiolytic effect of environmental enrichment is mediated via amygdalar CRF receptor type 1
Environmental Enrichment (EE) is known to have an anxiolytic effect in several animal models; however, the molecular mechanisms underlying these behavioral changes are not understood. Here, we demonstrated that the anxiolytic effect of EE is associated with alterations in the corticotropin-releasing factor receptor type 1 (CRFR1) expression levels in the limbic system. We found that the decrease in anxiety-like behavior following housing in enriched conditions was associated with very low levels of CRFR1 mRNA expression in the basolateral amygdala of C57BL/6 mice. We further demonstrated using a lentiviral-based system of RNA interference, that knockdown of CRFR1 mRNA expression in the basolateral amygdala induces a significant decrease in anxiety levels, similar to those achieved by EE nurture. Our data strongly suggest that reduced expression of CRFR1 mRNA levels in the basolateral amygdala mediates the effect of EE on anxiety-like behavior. (Sztainberg et al., The anxiolytic effect of environmental enrichment is mediated via amygdalar CRF receptor type 1. Mol. Psychiatry, (In Press), 2010).
Mice housed in environmental enrichment (EE) conditions (left panel) showed an anxiolytic-like phenotype, which was associated with a significant reduction in CRF receptor type 1 (CRFR1) expression in the basolateral amygdala (BLA). A lentiviral-based system of RNA interference was used to genetically mimic the environmental enrichment anxiolytic-like effect in mice housed under standard conditions. In vivo knockdown of CRFR1 mRNA expression in the BLA induced a significant decrease in anxiety-like behavior, similar to the effect achieved by EE nurture. Site of injection was confirmed by an enhanced green fluorescence protein (eGFP) reporter (right panel), co-expressed with the CRFR1 RNA interference sequence. (For further information on this figure, please refer to the article by Sztainberg et al., Molecular Psychiatry, In Press, 2010).
2. Environmental enrichment model for mice
Environmental enrichment is a combination of complex inanimate and social stimulation and generally consists of housing conditions that facilitate enhanced sensory, cognitive, motor and social stimulation relative to standard housing conditions. One of the most robust effects of environmental enrichment is the reduction of anxiety levels. However, the extreme variability in enrichment protocols may account for some of the inconsistencies in its effects and the variance among results reported by different laboratories. In this protocol, we describe a simple environmental enrichment strategy for the induction of a robust and replicable anxiolytic effect in mice. We provide detailed instructions on how to build an enrichment cage that was specially designed for easy manipulation, cleaning and observation by the experimenter. In addition, the different enrichment items, their order in the cage, the frequency of renewal and their cleaning and sterilization are described. The total length of the protocol is 6 weeks. (Sztainberg Y and Chen A. An environmental enrichment model for mice. Nature Protocols, (In Press) 2010).
Picture of the EE cage (a) Top view of the EE cage. The standard cage lid was released to show the feeder. (b) Side view of the EE cage. Note the EE cage lid specially designed to keep the feeder at the same height as in a standard mouse cage. (For further information on this figure, please refer to the article by Sztainberg & Chen, Nature Protocol, In Press, 2010).
