Art - Gould (J)

nature neuroscience • volume 2 no 3 • march 1999 The involvement of the hippocampal formation in learning has been recognized for decades1,2, but the cellular mechanisms underlying this association remain enigmatic. The hippocampal formation produces new neurons throughout adulthood in many vertebrates, from birds to primates3–8; however, although the number of neurons produced is high, the function of these cells is unknown. One possibility is that these new cells are important in hippocampus-dependent learning, a view consistent with reports that generalized environmental complexity enhances the number of new hippocampal neurons in adult birds and mice3,6. However, previous studies have not explored the possibility that hippocampus-dependent learning specifically alters the fate of adult-generated hippocampal neurons. To determine whether associative learning affects adult-generated hippocampal neurons, we examined the fate of new cells labeled with the thymidine analog bromodeoxyuridine (BrdU) in adult rats after a number of different behavioral manipulations. We used two different hippocampus-dependent tasks (classical conditioning of the eyeblink response using a trace protocol9–12 and spatial navigation learning in a Morris water maze13) and two hippocampus-independent learning tasks (classical eyeblink conditioning using a delay protocol9 and cue training in a Morris water maze13).