Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory

Trace memories are formed when a stimulus event becomes associated with another event that occurs later in time and is discontinuous with the first event. The formation of trace memories enhances the survival of newly generated neurons in the dentate gyrus of the adult hippocampus (Gould et al., 1999a). Here we tested whether the acquisition of trace memories early during training is sufficient to enhance cell survival. We also examined whether the new neurons affected by trace memory formation persist indefinitely or only as long as the hippocampus is necessary for the expression of those memories. Groups of adult rats were injected with bromodeoxyuridine (BrdU), a marker of dividing cells, and trained 1 week later with paired stimuli using a trace eyeblink conditioning task or exposed to the same number of unpaired stimuli. Cell survival was assessed after different numbers of training trials and survival periods after training. Overall cell survival was not enhanced by exposure to 200 trials of paired stimuli during trace conditioning. However, there was a positive correlation between performance of individual animals and cell survival. In addition, exposure to 800 trials of paired stimuli during trace conditioning increased the number of BrdU-labeled cells 60 d after training. The vast majority of these cells were neurons and coexpressed the neuronal markers class III β-tubulin or neuronal nuclei. These data suggest that individual differences in associative learning predict whether new neurons will survive and that once affected, these neurons remain for months and beyond the time when they are required for the retention of trace memories.