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Researchers are bringing the wild inside their laboratories. Compelled by studies that suggest animals' bodies and minds react to even minor changes in living conditions, scientists are decorating animal cage interiors to mimic the exterior world of nature, thus challenging lab animals to think and move.
A large, complex living space outfitted with objects that stimulate animals' mental and physical growth form the ideals of environmental enrichment (EE)--a field of study started by psychologists in the 1960s, which has now moved mainstream, particularly among neuroscientists. Advocates of EE say that providing multifaceted living conditions is essential to the mental and physical well-being of lab animals and could also influence the validity of experimental results. "You can argue whether your previous results are valid or not," says Vera Baumans, professor of laboratory animal science at the Karolinska Institute in Stockholm. "At KI we're going to find out if that is the case."
Not all labs take enrichment as seriously as the Karolinska Institute, but the growing interest in the relationship between environment and experimental results has converged with the influence of animal rights' groups on science policy, so that labs are becoming more aware than ever of animal care. "Effects from differential experiences have been found in species from fly to philosopher," says Mark Rosenzweig, professor emeritus of graduate studies at the University of California, Berkeley, and pioneer of applying environmental enrichment to laboratory testing. "Many investigators have come to realize that animals raised without sufficient stimulation do not develop full growth of brain or full behavioral capacities."
Emma Hockly, research fellow at Guy's Hospital, Kings College London, has found that even minimal enrichment, consisting of a plastic tunnel for running and food on the cage floor, for example, slows the development of symptoms of Huntington disease (HD) in mice.1 Creating a higher level of enrichment, by using a running wheel, tunnels, toys, gnawing sticks, and extra bedding, has helped stave off the decline of motor performance and further slow the advancement of HD. "There's kind of a rapid degeneration but there is still a marked improvement," in motor skills, Hockly says. The improvements are due to the cognitive and physical stimuli provided by an enriched environment: Animals with nothing to do in a life of captivity may turn to self-mutilating activities, says Elizabeth Gould, neuroscientist and professor at Princeton University, who works with primates.
INVENTING ENRICHMENT Psychologist Donald Hebb pioneered the field of environmental enrichment in the 1940s by raising rats in his home. Hebb found that his home provided a more challenging environment than that supplied through standard laboratory conditions, and the rats responded by displaying enhanced intelligence and superior problem solving skills.
In the early 1960s, a group led by Rosenzweig was using environmental enrichment when the team inadvertently challenged the long-held theory that the adult animal brain cannot show changes in volume as a result of learning or experience. Using rats housed 12 to a cage with stimulating objects, Rosenzweig compared learning ability to differences in brain chemistry. The rats housed in an enriched environment had increased activity of acetylcholinesterase (the enzyme that initiates the synaptic transmitter, acetylcholine), but Rosenzweig also found unexpected changes in cortical morphology: an 8% increase in thickness of the cerebral cortex, and an increased number of neurons and synapses. "We found that the cerebral cortex could vary with experience, something that had never before been demonstrated," Rozenzweig says.2
When neuroanatomist Marian C. Diamond joined the Rosenzweig group in 1961, the team found that these differential experiences in environment were also producing detailed changes in neuroanatomy, including alterations in neuron size, numbers of synaptic contacts, and branches of the dendritic tree.
This breakthrough led to subsequent discoveries by Bill Greenough, professor of psychology and psychiatry at the University of Illinois at Urbana-Champaign, who demonstrated that brain plasticity was not limited to neurons. He found that within the capillary system, the carrying capacity per neuron increased by nearly 100%. "Synapses were principally increased by learning, and vasculature capillaries were increased by activity, suggesting that different elements respond differently," Greenough explains.
UPDATING ENRICHMENT Because Rosenzweig's group challenged the dogma that adult brain measures were set and could not be increased, members of the biomedical community scoffed at such a startling discovery made by psychologists. "Our findings weren't new or important until a prominent scientist said that 'everyone already knew' that the brain is highly plastic," Rosenzweig says. Nevertheless, Rosenzweig's legacy lives on as environmental enrichment in experimentation continues at a pace even he says he couldn't have envisioned.
At Princeton, Gould has applied enriched living conditions in several of her studies of nonhuman primates. The cages in Gould's lab are 64 times the size mandated by the NIH for nonhuman primates, big enough for Gould to stand in, which is more representative of their natural home. The environment inside the cage is changed every other day, using different toys and live vegetation to recreate the natural environment of a rainforest. Tree branches with drilled holes allow the monkeys to forage for insects and fruit. "It's very expensive and very labor intensive to recreate environments," Gould says "but the animals are getting many more cognitive challenges interacting with the environment than the animals who just hang on the walls doing nothing."
The stimuli and pressures that come from living in an environment where animals socially interact and apply critical thinking in their daily routine, to find their meals, for example, are a crucial part of brain development. The enrichment has contributed to many of Gould's findings. In an enriched colony of marmosets, Gould saw changed parameters in every brain region, and in adult rhesus macaques, she observed increased neurogenesis in the dentate gyrus, and newly generated cells in the hippocampus.3
Gould says that environmental enrichment helps prevent stresses that can inhibit neurogenesis. "We know that if we manipulate small experiences in their lives, we can get fairly large changes in the brain," she says. "Simply put, animals living in deprivation don't make for a good control group."
Gould's lab, a veritable country club compared to the bare-bones environs of food and bedding lab animals often receive, demonstrates the importance of the interaction between the social and physical environment, although which aspect has a greater impact remains debatable. "In some ways it's like asking if height or width contributes more greatly to the area of a rectangle," Greenough says. Providing social partners appears to be the most significant input for reducing behavioral abnormalities. Yoland Smith, professor of neurology at Yerkes National Primate Research Center in Atlanta, keeps his monkeys housed singularly in large cages, allowing him to control variables such as food intake. But the cages are close enough that the animals can communicate.
COSTS OF COMPASSION Scientists such as Smith and Gould increasingly show the benefits of improving the social and physical environments for lab animals, the higher costs and the possibility of diminished standardization among experiments are contentious issues. Researchers may desire to provide the best facilities for their test subjects, but larger enclosures take up more real estate in the lab, and they raise the per diem costs of caring for the animals. Big cages also require a budget for furnishings, as a monkey with nothing to do in a larger cage isn't likely to show any change in behavior. Toys must be purchased frequently, as nonhuman primates, much like their human counterparts, become bored easily.
Some labs have done everything but hold bake sales to maintain favorable conditions. Gould's lab members and those in other departments often put in extra hours so that specialized staff need not be hired. In addition to cost, the use of lab space and toys to enrich the environment creates difficulties with standardization among labs. Encouraging animals to forage, nest, and play presents new experimental variables to be controlled. "Researchers try to create environments consistent between labs, but small changes in enrichment can have big effects," Hockly says. "It's so difficult to be sure that you're doing the same thing as other labs. You just have to make sure to be consistent in your own lab."
Baumans' work suggests that subtle differences in enrichment protocols can affect animals' responses to surgery, making standardization of those protocols significant. Baumans observed a difference between test groups living in the minimal environment of a small cage with the slight enrichment of sawdust, and those in an environment enriched with nesting material, a climbing grid, gnawing sticks, and a plastic tube.
"When you look at the physiology, the enriched and nonenriched will differ," Baumans says. "An animal in an environmental enrichment [program] will show more species-specific behavior because they can do more. They will be better learners." But, Baumans adds, researchers can aim for only relative standardization, as animals themselves may show differences before they even get to the lab. "We know that animals from different suppliers will also differ," Bauman says, "so you're getting completely different animals to begin with. People have said that enrichment increases variation, but an animal is not a test tube. There will always be variations."
Hal Cohen can be contacted at firstname.lastname@example.org.
1. E. Hockly et al., "Environmental enrichment slows disease progression in R6/2 Huntintgton's disease mice," Ann Neurol, 51:235-42, 2002.
2. D. Kretch et al., "Relations between brain chemistry and problem-solving among rats raised in enriched and impoverished environments," J Comp Physiol Psychol, 55:801-7, 1962.
3. E. Gould, C.G. Gross, "Neurogenesis in adult mammals: Some progress and problems," J Neurosci, 22:619-23, 2002.