Effect of dentate gyrus disruption on remembering what happened where.

Woon Ryoung Kim,Min Whan Jung,Jong Won Lee,June-Seek Choi,Sung-Hyun Lee,Woong Sun

doi:10.3389/fnbeh.2015.00170

Abstract

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.

Highlights

These results show that Bax knockout (Bax-KO) mice, as long as there was no interruption, could retain working memory of a previously visited location for a relatively long period of time
We have shown previously that spatial firing of hippocampal neurons in Bax-KO mice was dissociated from an external landmark, and that Bax-KO mice followed dead reckoning instead of landmarks when there was a mismatch between dead reckoning- and landmark-based prediction of a goal location (Lee et al, 2009, 2012b)
The present study shows that Bax-KO mice are impaired in using external sensory stimuli, and in remembering a previously visited location in navigating toward a rewarding location

Summary

Introduction

Hippocampus plays an essential role in encoding episodic (or episodic-like) memory (Scoville and Milner, 1957; Nadel and Moscovitch, 1997; Eichenbaum et al, 1999; Squire et al, 2004), which is the memory of a specific past event that occurred at a particular time and place (Morris, 2001; Clayton et al, 2001; Dere et al, 2006; Ferbinteanu et al, 2006; Eacott and Easton, 2010; Eichenbaum et al, 2012). Because inputs from the medial and lateral EC converge in the dentate gyrus (DG) and CA3, it has been proposed that the internally-generated spatial map is associated with external landmarks in the DG-CA3 network, forming a distinct spatial context for each environment (Redish and Touretzky, 1997; Hafting et al, 2005; O’Keefe and Burgess, 2005; Knierim et al, 2006, 2014; Witter and Moser, 2006; Gorchetchnikov and Grossberg, 2007; Leutgeb and Leutgeb, 2007)

Methods

Results

Conclusion