Lateral Entorhinal Cortex Lesions Impair Local Spatial Frameworks

Abstract

A prominent theory in the neurobiology of memory processing is that episodic memory is supported by contextually gated spatial representations in the hippocampus formed by combining spatial information from medial entorhinal cortex (MEC) with non-spatial information from lateral entorhinal cortex (LEC). However, there is a growing body of evidence from lesion and single-unit recording studies in rodents suggesting that LEC might have a role in encoding space, particularly the current and previous locations of objects within the local environment. Landmarks, both local and global, have been shown to control the spatial representations hypothesized to underlie cognitive maps. Consequently, it has recently been suggested that information processing within this network might be organized with reference to spatial scale with LEC and MEC providing information about local and global spatial frameworks respectively. In the present study, we trained animals to search for food using either a local or global spatial framework. Animals were re-tested on both tasks after receiving excitotoxic lesions of either the MEC or LEC. LEC lesioned animals were impaired in their ability to learn a local spatial framework task. LEC lesioned animals were also impaired on an object recognition (OR) task involving multiple local features but unimpaired at recognizing a single familiar object. Together, this suggests that LEC is involved in associating features of the local environment. However, neither LEC nor MEC lesions impaired performance on the global spatial framework task.

Keywords: allocentric; hippocampus; medial entorhinal cortex; navigation; object recognition; spatial memory.

Figure 1

(A) Illustration of a single test box with one high wall and three low walls. For the local task, only one test box was used with the arched doorway shut. For the global task, two identical test boxes were connected on either side of a starter box. Animals moved between boxes through the arched doorways in the middle of the high walls. (B) Schematic representation of the local task. The test box consisted of two 3D objects (local cues) in opposite corners and two pots of sand (rewarded/unrewarded) in the remaining corners. A black curtain surrounded the test box to eliminate global cues. (C) Schematic representation of the global task. One pot of sand each (rewarded/unrewarded) was placed in the center of each test box. Four large global landmarks were placed around the apparatus. (B,C) Arrows depict the two potential starting positions on each trial. The reward pot is highlighted with an asterisk. The thick black line represents the high wall of the test box.

Figure 2

(A) Schematic representation of medial entorhinal cortex (MEC) lesions for rats with the greatest (light gray) and least (dark gray) damage. Representations of coronal sections have been adapted from Paxinos and Watson (2007) at −8.28 mm, −8.04 mm, −7.80 mm and −7.68 mm, Bregma, from top to bottom, respectively. (B) Photographs of coronal sections of the largest MEC lesions from −8.28 mm, −8.04 mm, −7.80 mm and −7.68 mm Bregma (top to bottom).

Figure 3

(A) Schematic representation of lateral entorhinal cortex (LEC) lesions for rats with the greatest (light gray) and least (dark gray) damage. Representations of coronal sections have been adapted from Paxinos and Watson (2007) at −7.32 mm, −6.96 mm, −6.60 mm and −6.24 mm Bregma, from top to bottom, respectively. (B) Photographs of coronal sections of the largest LEC lesions from −7.32 mm, −6.96 mm, −6.60 mm and −6.24 mm Bregma (top to bottom).

Figure 4

(A) Average days to criteria score on the local and global task during the training phase, pre-surgery. (B) Average accuracy measure for the last 3 days pre-surgery on the local and global tasks. (C) Average accuracy measure for the last 3 days pre-surgery (left) and the first 3 days post-surgery (right) on the local task for LEC, MEC and sham groups. (D) Average accuracy measure for the last 3 days pre-surgery (left) and the first 3 days post-surgery (right) on the global task for LEC, MEC and sham groups. ***P < 0.001.

Figure 5

Average days to criteria mean difference score for MEC and LEC lesioned animals on the local (left) and global (right) task during the test phase, post-surgery. *P < 0.05, **P < 0.01.

Figure 6

(A) Average discrimination indices for the MEC, LEC and sham groups on the simple object recognition (OR) task. (B) Average re-exploration scores for the MEC, LEC and sham groups on the complex OR task. ^#P < 0.05, ^###P < 0.001, t-test vs. 0 (simple OR), t-test vs. 0 (complex OR).