Neurogenesis may relate to some but not all types of hippocampal-dependent learning

The hippocampal formation generates new neurons throughout adulthood. Recent studies indicate that these cells possess the morphology and physiological properties of more established neurons. However, the function of adult generated neurons is still a matter of debate. We previously demonstrated that certain forms of associative learning can enhance the survival of new neurons and a reduction in neurogenesis coincides with impaired learning of the hippocampal-dependent task of trace eyeblink conditioning. Using the toxin methylazoxymethanol acetate (MAM) for proliferating cells, we tested whether reduction of neurogenesis affected learning and performance associated with different hippocampal dependent tasks: spatial navigation learning in a Morris water maze, fear responses to context and an explicit cue after training with a trace fear paradigm. We also examined exploratory behavior in an elevated plus maze. Rats were injected with MAM (7 mg/kg) or saline for 14 days, concurrent with BrdU, to label new neurons on days 10, 12, and 14. After treatment, groups of rats were tested in the various tasks. A significant reduction in new neurons in the adult hippocampus was associated with impaired performance in some tasks, but not with others. Specifically, treatment with the antimitotic agent reduced the amount of fear acquired after exposure to a trace fear conditioning paradigm but did not affect contextual fear conditioning or spatial navigation learning in the Morris water maze. Nor did MAM treatment affect exploration in the elevated plus maze. These results combined with previous ones suggest that neurogenesis may be associated with the formation of some but not all types of hippocampal-dependent memories. (C) 2002 Wiley-Liss, Inc.