Developmental plasticity is the extent to which an organism can differ in morphology, physiology, and behaviour as a result of differences in the environment in the course of development. In rodents, it is well known that maternal and other environmental influences during early ontogeny can fundamentally change brain development and thus the physiological and behavioural responses they exhibit as adults. Therefore, the behavioural response of an animal in a particular test situation critically depends on the environmental background of that animal. Because environmental conditions during ontogeny can interact with the genotype of the animal in specific ways, behavioural phenotypes may be idiosyncratic to particular genotype x environment interactions. Moreover, inappropriate sensory inputs during ontogeny can disrupt the normal functioning of the brain. Thus, environmental conditions that overtax the animals' capacity to adapt may result in behavioural profiles that represent pathological artefacts.

Despite our knowledge of these relationships, environmental background is largely ignored in the behavioural phenotyping of mutant mice and, in fact, in much of animal experimentation in biomedical research. As a result, current approaches to the behavioural phenotyping of mutant mice are seriously flawed in two main ways. First, without systematic variation, standardization of the environmental background of the animals involves the risk of obtaining artefacts that are idiosyncratic to the particular study (1,2). For example, some studies reported behavioural effects of gene knockouts in mice that had been reared under standard housing conditions, but not in mice exposed to a more enriched environment or in postnatally handled animals. Thus, external validity of behavioural phenotypes might often be limited to a specific husbandry protocol, which makes it difficult to justify both the resources (money, manpower) and animals used for the research.

Secondly, increasing evidence indicates that current standard housing conditions for rodents impose serious constraints on behaviour and brain development of these animals, resulting in aberrant or maladaptive brain functions (3). For example, when mice are reared in barren standard cages they develop persistent stereotypic behaviours. Contrary to the commonly held belief that such stereotypies represent normal behavioural habits in a non-stimulating environment, recent evidence indicates that they are a symptom of cage-induced basal ganglia dysfunction. Again, this has serious implications for both the validity of the research and the well-being of the animals.

Providing animals with environmental conditions that meet their species-specific behavioural needs, and systematic variation of these conditions, therefore appears to be crucial in view of generating data that fulfil the requirements of good laboratory practice in terms of both scientific validity and animal welfare.

References

1. Würbel, H. 2000. Behaviour and the standardisation fallacy. Nat. Genet., 26, 263.
2. Würbel, H. 2002. Behavioral phenotyping enhanced - beyond (environmental) standardization. Genes Brain Behav., 1, 3-8.
3. Würbel, H. 2001. Ideal homes? - Housing effects on rodent brain and behaviour. Trends Neurosci., 24, 207-211.

© 2002 Noldus Information Technology bv