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Lack of anticipatory behavior in Gpr88 knockout mice showed by automatized home cage phenotyping.

ABSTRACT: Mouse models are widely used to understand genetic bases of behavior. Traditional testing typically requires multiple experimental settings, captures only snapshots of behavior and involves human intervention. The recent development of automated home cage monitoring offers an alternative method to study mouse behavior in their familiar and social environment, and over weeks. Here, we used the IntelliCage system to test this approach for mouse phenotyping, and studied mice lacking Gpr88 that have been extensively studied using standard testing. We monitored mouse behavior over 22?days in 4 different phases. In the free adaptation phase, Gpr88 -/- mice showed delayed habituation to the home cage, and increased frequency of same corner returns behavior in their alternation pattern. In the following nose-poke adaptation phase, non-habituation continued, however, mutant mice acquired nose-poke conditioning similar to controls. In the place learning and reversal phase, Gpr88-/- mice developed preference for the water/sucrose corner with some delay, but did not differ from controls for reversal. Finally, in a fixed schedule-drinking phase, control animals showed higher activity during the hour preceding water accessibility, and reduced activity after access to water was terminated. Mutant mice did not show this behavior, showing lack of anticipatory behavior. Our data therefore confirm hyperactivity, non-habituation and altered exploratory behaviors that were reported previously. Learning deficits described in other settings were barely detectable, and a novel phenotype was discovered. Home cage monitoring therefore extends previous findings and shows yet another facet of GPR88 function that deserves further investigation.

SUBMITTER: Maroteaux G

PROVIDER: S-EPMC6157014 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Project description:Numerous studies ascertained positive effects of enriched environments on the well-being of laboratory animals including behavioral, physiological and neurochemical parameters. Conversely, such conclusions imply impaired animal welfare and health in barren husbandry conditions. Moreover, inappropriate housing of laboratory animals may deteriorate the quality of scientific data. Recommendations for housing laboratory animals stipulate that cages should be enriched to mitigate adverse effects of barren housing. In this context, it is not only unclear what exactly is meant by enrichment, but also how the animals themselves interact with the various items on offer. Focal animal observation of female C57BL/6J mice either housed in conventional (CON) or enriched (ENR) conditions served to analyze the impact of enriching housing on welfare related behavior patterns including stereotypical, maintenance, active social, and inactive behaviors. CON conditions resembled current usual housing of laboratory mice, whereas ENR mice received varying enrichment items including foraging, housing and structural elements, and a running disc. Active and inactive use of these elements was quantitatively assessed. CON mice showed significantly more inactive and stereotypical behavior than ENR mice. ENR mice frequently engaged with all enrichment elements, whereby riddles to obtain food reward and the running disc preferably served for active interactions. Offering a second level resulted in high active and inactive interactions. Structural elements fixed at the cagetop were least attractive for the mice. Overall, the presented data underline the positive welfare benefits of enrichment and that mice clearly differentiate between distinct enrichment types, demonstrating that the perspective of the animals themselves should also be taken into account when specifying laboratory housing conditions. This is particularly important, as the ensuring of animal welfare is an essential prerequisite for reliable, reproducible, and scientifically meaningful results.

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Lack of anticipatory behavior in Gpr88 knockout mice showed by automatized home cage phenotyping.

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