The Role of the Dentate Gyrus in a Spatial Working Memory Task in Healthy and Epileptic Mice

Maryam Pasdarnavab1, Laura Kück1, Fethullah Gerin1, Laura Ewell1

1 Institute of Experimental Epileptology and Cognition Research, University of Bonn Medical Center

The dentate gyrus (DG) of the hippocampus is often considered to perform the first step in the processing of information that ultimately leads to the production of episodic memories, and recently has been shown to support spatial working memory in rodents. The DG is severely altered in temporal lobe epilepsy (TLE), exhibiting cell death, and axon rewiring. Little is known about how these pathological changes would affect DG memory processes. Here, we utilized the supra-hippocampal Kainic acid (KA) mouse model of TLE to investigate this. Immunohistology demonstrated a decrease in CA1 cell layer thickness and granule cell dispersion selectively in the hippocampus ipsilateral to the KA injection (n = 6). Consistent with the hypothesis that hippocampal pathology will confer memory deficits, we observe a working memory deficit in KA mice in a delayed-alternation spatial working memory task. The number of correct choices during 5 days of the test phase for KA mice is 59.23, 55, 60.38, 60.38, 71.92 and for control mice is 79.37, 73.75, 70, 69.37, 72.5 (n=8 Control and n=11 KA injected animals). We further investigated the neural mechanisms of the working memory deficit by performing high-density single-unit recordings from CA1 and the dentate gyrus during task performance. Prevalent interictal activities were recorded from CA1 and DG during the task. Furthermore, preliminary results show DG place cell remapping between continuous and delay versions of the task, and current analysis are aimed at understanding whether this computation is altered in KA versus control animals.