We here report that voluntary wheel running led to a regional
increase in the number of newly generated cortical microglia. We
asked how adult cortical cell genesis would respond to environ-
mental enrichment and physical activity, both stimuli that robustly
induce adult hippocampal neurogenesis. After labeling proliferating
cells with bromodeoxyuridine (BrdU) and immunohistochemical
detection of BrdU, we found that both experimental paradigms did
not result in general effects on cell proliferation and cell genesis in
the neocortex. However, there were regionally and layer specific
changes in the number of BrdU marked cells, both 1 day and 4 weeks
after BrdU. Environmental enrichment led to a significant increase in
the number of new astrocytes in layer 1 of the motor cortex.
Voluntary wheel running, in contrast, caused an induction in the
proliferation of microglia in superficial cortical layers of several
brain regions. Under no condition was the number of new oligo-
dendrocytes measurably enhanced. In contrast to the hippocampus,
we did not find any new neurons in the cortex. The physiological
‘activation’ of microglia adds a new aspect to the question of
microglial function in the healthy brain and of how adult brain cells
can plastically react to physiological stimuli.
Introduction
Cell genesis in the adult mammalian neocortex has received
considerable interest, because it was claimed that new neurons
could be generated in the adult cerebral cortex (Gould et al.,
1999, 2001). The scientific debate that arose (Nowakowski and
Hayes, 2000; Grassi Zucconi and Giuditta, 2002; Rakic, 2002)
took place in the light of earlier reports on adult neurogenesis in
other brain regions (Altman and Das, 1965; Cameron et al.,
1993; Lois and Alvarez-Buylla, 1993; Kuhn et al., 1996).
In the dentate gyrus of the adult hippocampus, new neurons
are continually generated from a local population of stem or pro-
genitor cells. Adult neurogenesis and its regulation can be linked
to hippocampal function (Kempermann, 2002; Kempermann
an