Previous research has shown that some associative learning tasks prevent the death of new neurons in the adult hippocampus. However, it is unclear whether it is mere exposure to the training stimuli that rescues neurons or whether successful learning of the task is required for enhanced neuronal survival. If learning is the important variable, then animals that learn better given the same amount of training should retain more of the new cells after learning than animals that do not learn as well. Here, we examined the effects of training versus learning on cell survival in the adult hippocampus. Animals were injected with BrdU to label a population of cells and trained one week later on one of two trace conditioning tasks, one of which depends on the hippocampus and one that does not. Increases in cell number occurred only in animals that acquired the learned response, irrespective of the task. There were significant correlations between acquisition and cell number, as well as between asymptotic performance and cell number. These data support the idea that learning and not simply training increases the survival of the new cells in the hippocampus.

BACKGROUND: Numerous studies have implicated neurogenesis in the hippocampus in animal models of depression, especially those related to controllability and learned helplessness. Here, we tested the hypothesis that uncontrollable but not controllable stress would reduce cell proliferation in the hippocampus of male and female rats and would relate to the expression of helplessness behavior. METHODS: To manipulate controllability, groups of male and female rats were trained in one session (acute stress) or over seven sessions (repeated stress) to escape a footshock, whereas yoked control subjects could not escape but were exposed to the same amount of stress. Cell proliferation was assessed with immunohistochemistry of bromodeoxyuridine (BrdU) and immunofluorescence of BrdU and neuronal nuclei (NeuN). Separate groups were exposed to either controllable or uncontrollable stress, and their ability to learn to escape during training on a more difficult task was used as a behavioral measure of helplessness. RESULTS: Acute stress reduced cell proliferation in males but did not affect proliferation in the female hippocampus. When animals were given the opportunity to learn to control the stress over seven days, males produced more cells than the yoked males without control. Repeated training with controllable stress did not influence proliferation in females. Under all conditions, males were more likely than females to express helplessness behavior, even males that were not previously stressed. CONCLUSIONS: The modulation of neurogenesis by controllability was evident in males but not in females, as was the expression of helplessness behavior, despite the fact that men are less likely than women to experience depression.