Dismantling the Papez circuit for memory in rats
- Cardiff University, United Kingdom
Figures
Figure 1
Photomicrographs depicting typical lesions.
(A) Acetylcholinesterase-stained section showing ventral tegmental nucleus of Gudden lesion. (B) Acetylcholinesterase-stained section showing the ventral tegmental nucleus of Gudden (indicated by the arrows) in an intact animal. (C) Acetylocholinesterase staining in the anteroventral thalamic nuclei in a ventral tegmental nucleus lesion rat; and (D) a surgical control rat; (E) Nissl-stained section showing mammillothalamic tract lesion, the arrows indicate the lesion. The intact postcommissural fornix is highlighted within the circles. (F) Nissl-stained section showing postcommissural fornix lesion, the arrows indicate the lesion and the intact mammillothalamic tract is highlighted within the circles. (G) Mammillary bodies from a surgical control; (H) Mammillary body atrophy following postcommissural fornix lesion. (I) A higher magnification of (G) showing Nissl-stained cells in the medial mammillary nucleus of a surgical control shown. (J) A higher magnification of (H) showing increased cell packing in the medial mammillary nucleus following a post commissural fornix lesion. Numbers indicate distance in millimeters from bregma. Scale bar: (A–H), 500 μm; (I–J), 100 μm.
Figure 2
T-maze alternation.
(A). Experimental design for the three stages: solid lines indicate the forced sample phase while dashed lines indicate the correct response in the choice phase. By placing a barrier at the entrance of the arm access to an arm could be blocked (effectively turning the cross-maze into a T-maze configuration; this is illustrated by hatching). Initial training on the task (Stage 1) permitted the use of multiple strategies supporting alternation, that is allocentric, intra-maze, idiothetic, direction alternation (with reference to a known bearing). The task was then systematically modified in order to prevent the use of intra-maze cues (Stage 2) or the use of intra-maze and distal allocentric cues (Stage 3). These manipulations included using two mazes instead of one (Stage 2 and 3) or running in the dark, as illustrated with the gray background (Stage 3); (B) Mean percentage of correct choices (±SEM) for all three stages; (C) percentage of correct choices for the ‘same place’ and ‘different place’ trials in Stages 2 and 3. The vertical lines depict the standard error of the mean. Abbreviations: p; Sham, surgical control; *Significant difference between VTNx and Sham group (p<0.05); **Significant difference between VTNx and Sham group (p<0.01); §Significant difference between MTTx and Sham group (p<0.05); §§Significant difference between MTTx and Sham group (p<0.01); +Significant difference between PCFx and MTTx (p<0.05); ^Significant difference between PCFx and VTNx (p<0.05).
Figure 3
Radial-arm maze task.
(A) Mean number of errors (±SEM). First five blocks represent acquisition of the tasks and the final two blocks include rotation of the maze; (B) Mean number of correct entries in first eight arm choices (±SEM) during acquisition (first five blocks) and rotation (final two blocks); *Significant difference between VTNx and Sham group (p<0.05); **Significant difference between VTNx and Sham group (p<0.01); §Significant difference between MTTx and Sham group (p<0.05); §§Significant difference between MTTx and Sham group (p<0.01); +Significant difference between PCFx and MTTx (p<0.05); ^Significant difference between PCFx and VTNx (p<0.05).
Figure 4
Geometric discrimination in the water-maze.
(A) A schematic of the platform positions for the half of the animals (i.e., short wall to the right of long wall). (B) Mean escape latencies (±SEM) for task acquisition. (C) Probe performance. The platforms are removed from the pool and the rat is allowed to swim for 60s. The mean times spent (±SEM) in the correct corners and the incorrect corners are presented.
Figure 5
Mean c-Fos-positive cell counts (±SEM).
(A) Retrosplenial cortex and hippocampal formation (dentate gyrus, CA1, CA3); (B) Frontal cortices (infralimbic cortex and prelimbic cortex) and somatosensory cortex. (C) Supramammillary nuclei, lateral and medial septum. *Significant difference between VTNx and Sham group (p<0.05); **Significant difference between VTNx and Sham group (p<0.01); §Significant difference between MTTx and Sham group (p<0.05); §§Significant difference between MTTx and Sham group (p<0.01); ++Significant differences between PCFx (p<0.01); ^Significant difference between PCFx and VTNx (p<0.05).
Figure 6
Photomicrographs of Fos-positive nuclei in the retrosplenial cortex in the four groups: (A) mammillothalamic tract lesion (B) ventral tegmental nucleus of Gudden lesion; (C) descending postcommissural fornix lesion group (D) surgical control. The darkly stained cells are Fos-postitive neurons. The loss of distinctive c-Fos staining in layer two can been seen in the mammillothalamic tract lesion (A) and ventral tegmental nucleus of Gudden (B). Scale bar, 500 μm.
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Dismantling the Papez circuit for memory in rats
eLife 2:e00736.
https://doi.org/10.7554/eLife.00736
