New neurons are formed in the dentate gyrus of the mammalian hippocampus
throughout adulthood. Rates of adult neurogenesis can be manipulated by
pharmacological and environmental factors. Specifically, two factors that lead to
increased neurogenesis are the antidepressant fluoxetine which increases the
proliferation of neural progenitor cells and environmental enrichment which increases
neuronal survival. Although the putative function of adult neurogenesis is unknown,
there is accumulating evidence that it plays a role in hippocampal-dependent learning
and memory and as a self-repair response following brain insult. The aim of the present
study was investigate whether increasing neurogenesis in rats could promote a
recovery of spatial function following dentate gyrus damage. Intradentate infusions of
colchcine selectively ablated the majority of dorsal dentate gyrus granule cells. Rats
where then tested on the Morris water maze and matched to treatment groups. In the
treatment paradigm aimed at increasing rates of neurogenesis, rats were given daily
saline or fluoxetine injections and either lived in standard housing or a novel enriched
environment for 5 weeks with BrdU injections occurring in the middle. Ki67-staining
revealed a decrease in cell proliferation associated with the enriched environment.
Doublecortin-staining revealed that fluoxetine increased cell survival in the standard
housing. BrdU/NeuN-colabeling qualitatively revealed that neurogenesis did occur in the
damaged dentate gyrus, but at a low rate. Overall, dentate gyrus lesions significantly
decreased the proliferation and survival of new neurons following treatment. We
concluded that the colchicine dose used profoundly disrupted the neurogenic niche and that the enriched environment was inhibiting proliferation because it was more stressful
than the standard housing. In the post-treatment behavioral testing, lesion rats had
significant spatial memory deficits but did improve and enriched rats improved more
than standard housed rats. On the probe test, lesion rats outperformed sham rats and
lesion rats in the enriched environment outperformed all other rats on target search but
not target crossings which may be interpreted as an increased resistance to extinction
