Recent and remote retrograde memory deficit in rats with medial entorhinal cortex lesions

Abstract

The hippocampus is critically involved in the acquisition and retrieval of spatial memories. Even though some memories become independent of the hippocampus over time, expression of spatial memories have consistently been found to permanently depend on the hippocampus. Recent studies have focused on the adjacent medial entorhinal cortex (MEC), as it provides major projections to the hippocampus. These studies have shown that lesions of the MEC disrupt spatial processing in the hippocampus and impair spatial memory acquisition on the watermaze task. MEC lesions acquired after learning the watermaze task also disrupt recently acquired spatial memories. However, the effect of MEC lesions on remotely acquired memories is unknown. The current study examined the effect of MEC lesions on recent and remote memory retrieval using three hippocampus-dependent tasks: the watermaze, trace fear conditioning, and novel object recognition. MEC lesions caused impaired retrieval of recently and remotely acquired memory for the watermaze. Rats with MEC lesions also showed impaired fear memory when exposed to the previously conditioned context or the associated tone, and this reduction was seen both when the lesion occurred soon after trace fear condition and when it occurred a month after conditioning. In contrast, MEC lesions did not disrupt novel object recognition. These findings indicate that even with an intact hippocampus, rats with MEC lesions cannot retrieve recent or remote spatial memories. In addition, the involvement of the MEC in memory extends beyond is role in navigation and place memory.

Keywords: Consolidation; Entorhinal; Hippocampus; Memory; Navigation; Rat.

Figure 1.. Extent of MEC lesions versus sham tissue

A. Photographs through the rat medial entorhinal cortex (MEC) at three sagittal levels (lateral to medial) for rats with MEC or sham lesions. The letters around the sham tissue section in the top row identifies the orientation of the sections (d, dorsal; v, ventral; a, anterior; p, posterior). The black arrows indicate the dorsal and ventral borders of the MEC. Scale bars below each tissue section indicate 1 mm.

Figure 2.. Retrieval of recently and remotely acquired watermaze platform location impaired after MEC lesions.

Probe trial performance measuring the percentage of time that each rat spent in the platform location (A) and in the target quadrant (B) in rats that had received medial entorhinal cortex (MEC) or sham lesions either 1–3 days (recent) or 1 month (remote) after training. Dashed lines indicate chance performance for the platform location and quadrant, which was 4% and 25%, respectively. Rats with MEC lesions were impaired at retrieving the platform location and target quadrant regardless of whether the training occurred 1–3 days before or 1 month before surgery. Sham rats performed above chance for all measures, whereas MEC-lesioned rats only performed above chance in the recent memory condition. Error bars indicate SEM. Asterisks indicate difference from sham group (* p < 0.05, ** p < 0.01, *** p < 0.001). Carets indicate performance above chance (p < 0.05).

Figure 3.. Retrieval of recently and remotely acquired fear memory impaired after MEC lesions.

Mean percent freezing to the previously conditioned context (A) or to the associated tone (B) during 8 minute retention tests for 5 discontiguous tone-shock pairs. Rats received medial entorhinal cortex (MEC) or sham lesions either 1–3 days (recent) or 1 month (remote) post-conditioning. Rats with MEC lesions showed impaired fear memory when exposed to the previously conditioned context or the associated tone regardless of whether conditioning occurred 1–3 days before or 1 month before surgery. Error bars indicate SEM. Asterisks indicate difference from sham group (* p < 0.05, ** p < 0.01, # p = 0.051).

Figure 4.. Novel object recognition was not impaired following MEC lesions.

Rats with sham (white bar) and medial entorhinal cortex (MEC; black bar) lesions performed equally and better than chance on the novel object recognition task. Dashed line indicates chance performance of 50%. Error bars indicate SEM.