Adult neurogenesis mediates forgetting of multiple types of memory in the rat

The formation and retention of hippocampus-dependent memories is impacted by neurogenesis, a process that involves the production of new neurons in the dentate gyrus of the hippocampus. Recent studies demonstrate that increasing neurogenesis after memory formation induces forgetting of previously acquired memories. Neurogenesis-induced forgetting was originally demonstrated in mice, but a recent report suggests that the same effect may be absent in rats. Although a general species difference is possible, other potential explanations for these incongruent findings are that memories which are more strongly reinforced become resilient to forgetting or that perhaps only certain types of memories are affected. Here, we investigated whether neurogenesis-induced forgetting occurs in rats using several hippocampal dependent tasks including contextual fear conditioning (CFC), the Morris Water Task (MWT), and touchscreen paired associates learning (PAL). Neurogenesis was increased following training using voluntary exercise for 4 weeks before recall of the previous memory was assessed. We show that voluntary running causes forgetting of context fear memories in a neurogenesis-dependent manner, and that neurogenesis-induced forgetting is present in rats across behavioral tasks despite differences in complexity or reliance on spatial, context, or object memories. In addition, we asked whether stronger memories are less susceptible to forgetting by varying the strength of training. Even with a very strong training protocol in the CFC task, we still observed enhanced forgetting related to increased neurogenesis. These results suggest that forgetting due to neurogenesis is a conserved mechanism that aids in the clearance of memories. Significance StatementRecent evidence indicates that hippocampal neurogenesis mediates forgetting of older memories and enhances encoding of new memories free of proactive interference. This evidence comes from multiple rodent species, behavioral tasks, and methods of increasing neurogenesis. However, a recent paper by (Kodali et al. 2016) found that voluntary exercise-induced neurogenesis did not cause forgetting in the Morris Water Task in rats. The results call into question whether the phenomenon is a conserved function of neurogenesis across species. In the present study, we show that voluntary running causes robust forgetting in rats in a neurogenesis-dependent manner and that the effect is present across three different behavioral tasks, confirming the existence of the phenomenon in rats and adding to the growing evidence that forgetting is a conserved function of hippocampal neurogenesis.