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Santoso, Ariane (2009): Cell proliferation and cell survival in the dentate gyrus of adult mice under naturalistic conditions. Dissertation, LMU München: Faculty of Biology
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Abstract

Throughout life, new cells are generated in the mammalian brain and incorporated as functional neurons in the networks of the olfactory bulb and the dentate gyrus (DG) of the hippocampal formation. So far proliferation and survival rates of newly generated cells in the adult DG have been investigated in commonly used and rather simple behavioral experiments like the Morris water maze, fear and trace conditioning, a running wheel and small enriched environments. Some of these studies gave evidence for an influence of single factors on neurogenesis, like physical activity, complexity of environment or associative learning. Results from laboratory experiments cannot directly be translated into the natural situation, because the relevance of these factors for animals in the wild is different from that for animals under laboratory conditions. Additionally, naturally an animal lives under a combination of several factors. Hence, we cannot derive the relevance of adult neurogenesis for wild-living animals from these studies. The aim of this study was to examine neuronal plasticity in a naturalistic environment with respect to factors that have the capability to influence neurogenesis separately and under laboratory conditions. Therefore, I compared cell proliferation and survival of newborn cells in DG of adult mice at different complexity levels of a naturalistic environment. Large enclosures equipped with computer-controlled water dispensers represented an environment near to nature, in which physical activity and exploration were possible and required. Foraging behavior was the basis for the investigation of the role of associative learning under naturalistic conditions. The extensive automation of the setup allowed for maximum avoidance of disruptions and interference of mouse behavior by the experimenter. With respect to this aspect, a new method for oral application of the proliferation marker BrdU via computer-controlled dispensers was established. In a naturalistic environment, mice expressed distinct exploratory behavior and optimized their foraging following the variation of water dispenser qualities. Surprisingly, neither exploring novel water resources nor spatial learning of positions of profitable resources lead to a change in the rate of neurogenesis. From the finding, that running induced a marked increase of proliferation rate when performed in a running wheel but not when performed in a naturalistic environment, the question arose if the type physical activity is critical. The comparison of running in a wheel with running in plane showed that the proliferation rate is independent from type of locomotion but strongly correlates with the extent of running activity. The pro-proliferative effect of running occurs acute and persists for at least 3, but not more than 5 days. Wheel running acts as a reliable promoter of cell proliferation in mice, but also represents a rather unnatural form of physical activity. Motivation for exercise as well as extent of exercise differ substantially between running wheel and natural locomotion. The results of this work indicate that the relevance of adult neurogenesis for natural behavior should be valuated with caution. In everyday life, the lifelong production of new cells in DG seems to function for the maintenance of a certain amount of neuronal resources rather than for the situational production of new neurons.