Changing the rate and hippocampal dependence of trace eyeblink conditioning: Slow learning enhances survival of new neurons

Trace eyeblink conditioning in which a conditioned stimulus and unconditioned stimulus are separated by a gap, is hippocampal dependent and can rescue new neurons in the adult dentate gyrus from death (e.g., Beylin et al., 2001 and Gould et al., 1999). Tasks requiring more training trials for reliable expression of the conditioned response are most effective in enhancing survival of neurons (Waddell & Shors, 2008). To dissociate hippocampal dependence from acquisition rate, we facilitated hippocampal-dependent trace eyeblink conditioning in two ways: a shorter trace interval and signaling the intertrial interval with a post-US cue. Trace conditioning with a shorter trace interval (250 ms) requires an intact hippocampus, and acquisition is faster relative to rats trained with a 500 ms trace interval (e.g., Weiss et al., 1999). Using excitotoxic hippocampal lesions, we confirmed that eyeblink conditioning with the 250 or 500 ms trace interval is hippocampal dependent. However, training with the post-US cue was not hippocampal dependent. The majority of lesion rats in this condition reached criterion of conditioned responding. To determine whether hippocampal dependence is sufficient to rescue adult-generated neurons in the dentate gyrus, rats were injected with BrdU and trained in one of the three trace eyeblink arrangements one week later. Of these training procedures, only the 500 ms trace interval enhanced survival of new cells; acquisition of this task proceeded slowly relative to the 250 ms and post-US cue conditions. These data demonstrate that rate of acquisition and not hippocampal dependence determines the impact of learning on adult neurogenesis.

Research highlights
► Learning can enhance survival of newly generated cells in the adult hippocampus.
► Tasks that are effective in promoting survival are typically slowly acquired and require an intact hippocampus.
► Here, we demonstrate that hippocampal dependence is not sufficient.
► Trace eyeblink conditioning with an arrangement that is more easily acquired does not rescue newly generated cells from death.
► Addition of a third discontiguous cue can render trace eyeblink conditioning independent of the hippocampus, and does not promote survival of new cells.