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Low-stimulus and restrictive housing can cause the development of a wide variety of behavioral disorders. These are considered indicators of impaired welfare and are associated with changes in the central nervous system. In scientific experiments, such pathological abnormalities can affect the experimental results. Therefore, good animal welfare is central to the reliability and thus the quality of animal experiments. However, the adoption of improved husbandry systems is biased by the concern that abandoning restrictive but fully controllable husbandry practices will lead to an increase in data variability.
Here, we investigated whether long-term housing in a conventional, restrictive housing system leads to behavioral abnormalities and neurological impairment compared to housing in an enriched cage environment as well as in a more species-appropriate housing in a semi-natural environment. Furthermore, we aim to understand how and to what extent variability in behavioral, morphological, physiological, and neuroanatomical data unfolds over time and whether variability is affected by housing conditions. Female C57Bl/6J mice were housed for 22 month in conventional cages (CON, n=12), enriched cages (ENR, n=12) and a semi-natural environment (SNE, n=20). We recorded the activity and spatial distribution of animals in the
SNE by radio-frequency identification. Neurophysiological outcome measures included hippocampal volumetry, differential analysis of neuronal cell formation and differentiation using proliferation markers CldU and IdU, and morphometric analysis neurons in the hippocampus and amygdala. Focal animal observation revealed that CON mice showed significantly more inactive and stereotypic behavior than ENR mice. SNE mice showed no stereotypic behavior. These behavioral abnormalities were associated by distinct impairments in brain morphology and physiology. In SNE animals, we detected an increase of diversification in roaming behavior over time with stabilizing activity patterns at the individual level. This suggests that individual
differences do indeed emerge and stabilize over time. Most interestingly, the variability of data from animals from the ENR and SNE systems did not exceed that of animals from the conventional systems, nor did it exceed literature data obtained from mice living under conventional laboratory conditions.
We conclude that species-appropriate housing of laboratory animals is crucial to prevent the emergence of behavioral disorders and neurological impairments. Furthermore, improving animal welfare through changes in husbandry conditions do not lead to a deterioration in data quality.