Strain differences in neurogenesis and activation of new neurons in the dentate gyrus in response to spatial learning

Adult neurogenesis continues throughout life in the mammalian hippocampus and evidence suggests that adult neurogenesis is involved in hippocampus-dependent learning and memory. Numerous studies have demonstrated that spatial learning enhances neurogenesis in the hippocampus but few studies have examined whether enhanced neurogenesis is related to enhanced activation of new neurons in response to spatial learning. Furthermore, the majority of these studies have utilized Sprague-Dawley (SD) rats. However, Long-Evans and Sprague-Dawley rats have been reported to have different learning abilities. In order to determine whether these strains exhibit a similar enhancement of neurogenesis and new neuronal activation in response to spatial learning we tested both strains in a hippocampus-dependent or hippocampus-independent version of the Morris water task (MWT) and then compared levels of neurogenesis and activation of these new cells in the hippocampus. Here we show that despite equivalent performance in the MWT, spatial learning produced a different effect on neurogenesis in each strain. Spatial learning increased cell survival and the number of immature neurons in SD rats compared to cage control and cue-trained rats. In Long-Evans (LE) rats however, spatial learning increased cell survival (BrdU-labeling) but did not increase the number of immature neurons (doublecortin-labeling). Furthermore, we report here an intriguing difference in the activation of new neurons (using the immediate early gene product zif268) in SD versus LE rats. In SD rats we show that spatial learning increases the percentage of doublecortin-labeled cells that are activated during a probe trial. Conversely, in LE rats spatial learning increased the activation of BrdU-labeled but not doublecortin-labeled cells. This interesting difference suggests that different ages or maturational stages of cells are recruited by spatial learning in the two strains. These findings may lead to a better understanding of how and why neurogenesis is regulated by spatial learning.