Task difficulty in the Morris water task influences the survival of new neurons in the dentate gyrus.

Adult neurogenesis continues throughout life in the mammalian hippocampus. The precise function of the adult generated neurons remains uncertain although there is growing evidence that they are involved in hippocampus-dependent learning and memory. Training rats on a hidden platform version of the Morris water task has been shown to increase or decrease the survival of newly produced cells in the dentate gyrus (DG) compared to training on a visible platform version. Here we investigated whether the difficulty of the task is related to the degree or direction of the change in neurogenesis. We trained rats on either a visible platform version of the Morris water task or one of three different hidden platform paradigms: four training trials per session version, two training trials per session, and reduced-cue (a version in which the majority of the distal cues were removed from the room). BrdU was administered 6 days prior to training and rats were perfused 24 h after the last training session. As expected, training on the four trial hidden platform version increased cell survival compared to training on the visible platform version. However, training on the more difficult reduced-cue hidden platform version resulted in a decrease in cell survival. Rats that received fewer trials per session did not differ in terms of cell survival in comparison to rats trained on the visible platform version. These findings demonstrate that altering the difficulty of the spatial task has an impact on the corresponding change in cell survival. The lack of obvious distal cues likely changed the strategy used by the rats to determine the location of the platform and resulted in a decrease, instead of an increase in cell survival in the hippocampus. In conclusion, different types of hippocampus-dependent learning can differentially impact cell survival.

Epp JR ，Haack AK ，Galea LA 《-》

Hippocampus-dependent strategy choice predicts low levels of cell proliferation in the dentate gyrus.

Epp JR ，Galea LA 《-》

Hippocampus-dependent learning promotes survival of new neurons in the dentate gyrus at a specific time during cell maturation.

Epp JR ，Spritzer MD ，Galea LA 《NEUROSCIENCE》

Activation and survival of immature neurons in the dentate gyrus with spatial memory is dependent on time of exposure to spatial learning and age of cells at examination.

Neurogenesis continues to occur throughout life in the dentate gyrus of the hippocampus and may be related to hippocampus-dependent learning. We have recently reported that there is an enhancement of neurogenesis in the hippocampus only when BrdU is administered 6 days prior to starting spatial training but not when training started either 1 day or 11 days following BrdU administration. In that study, all rats were perfused on day 16 after BrdU injection in order to compare cells of the same age (i.e. 16 day old cells) and thus the survival time after learning was different between groups. This study was designed to address whether the amount of time that passed following training could also contribute to the effects of spatial learning on hippocampal neurogenesis and whether there was differential new neuron activation in response to spatial learning that depended on the age of new cells at the time of spatial learning. Here we tested whether a survival period of 5 days following spatial learning at either 1-5, 6-10 or 11-15 days following BrdU administration would alter cell survival and/or activation of new neurons. Our results indicate that 5 days after training in the Morris water task cell survival is unaltered by training on days 1-5, increased by training at days 6-10 and decreased when training occurs on days 11-15. Furthermore spatial learners trained on days 6-10 or 11-15 show greater activation of new neurons compared to cue-trained rats during a probe trial 5 days after training. In addition, rats trained on the spatial task on days 11-15 had a greater number of activated new neurons compared to rats trained on the spatial task on days 6-10. These results suggest there is a gradual removal of older BrdU-labeled new neurons following spatial learning perhaps due to a competitive interaction with a population of younger BrdU-labeled new neurons.

Epp JR ，Haack AK ，Galea LA 《-》

Working memory task decreases the survival of newly born neurons in hippocampus.

Throughout life new neurons are generated in dentate gyrus of hippocampus. Previous studies have found that spatial tasks can rescue newly born neurons from death. However, it is still unknown whether new neurons are similarly affected by all types of hippocampal-dependent tasks. Here we investigated the possible effects of working memory task (WMT) on immature neurons. Mice were trained in reference memory task and WMT respectively. The reference memory task used the classical hidden platform (HP) water maze task, while WMT used a delayed matching-to-place (DMTP) water maze task. Bromodeoxyuridine (BrdU) was administrated during the early or late phase of training, or 1week prior to training, in order to label dividing proliferating cells. After water maze training, the number of BrdU-labeled cells in dentate gyrus of hippocampus was compared. In addition, hippocampal brain-derived neurotrophic factor (BDNF) and Notch 1 receptor were characterized using Western blot. Serum corticosterone levels were also measured using enzyme immunoassay. Results showed that HP task and DMTP task did not change the number of BrdU-labeled cells produced during the early or late phase of training. As expected, the HP task increased the number of BrdU-labeled cells produced 1 week prior to training. However, DMTP task decreased the number of BrdU-labeled cells produced 1 week prior to training. Both tasks lead to a significant increase in serum corticosterone levels and did not change the expression of BDNF and Notch 1 receptor in hippocampus. Taken together, these results demonstrate that WMT has different effects on survival of immature neurons, and therefore suggests immature neurons may have more than one role depending on the demands of the tasks.

Xu Z ，Li J ，Zhang F ，Wu Y ，Gao Y ，Liang J ，Zhang C ... -  《-》