Effect of dentate gyrus disruption on remembering what happened where.

Our previous studies using Bax knockout (Bax-KO) mice, in which newly generated granule cells continue to accumulate, disrupting neural circuitry specifically in the dentate gyrus (DG), suggest the involvement of the DG in binding the internally-generated spatial map with sensory information on external landmarks (spatial map-object association) in forming a distinct spatial context for each environment. In order to test whether the DG is also involved in binding the internal spatial map with sensory information on external events (spatial map-event association), we tested the behavior of Bax-KO mice in a delayed-non-match-to-place task. Performance of Bax-KO mice was indistinguishable from that of wild-type mice as long as there was no interruption during the delay period (tested up to 5 min), suggesting that on-line maintenance of working memory is intact in Bax-KO mice. However, Bax-KO mice showed profound performance deficits when they were removed from the maze during the delay period (interruption condition) with a sufficiently long (65 s) delay, suggesting that episodic memory was impaired in Bax-KO mice. Together with previous findings, these results suggest the role of the DG in binding spatial information derived from dead reckoning and nonspatial information, such as external objects and events, in the process of encoding episodic memory.