Cell proliferation and cell survival in the dentate gyrus of adult mice under naturalistic conditions

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.