Paradoxical facilitation of object recognition memory after infusion of scopolamine into perirhinal cortex: implications for cholinergic system function

Abstract

The cholinergic system has long been implicated in learning and memory, yet its specific function remains unclear. In the present study, we investigated the role of cortical acetylcholine in a rodent model of declarative memory by infusing the cholinergic muscarinic receptor antagonist scopolamine into the rat perirhinal cortex during different stages (encoding, storage/consolidation, and retrieval) of the spontaneous object recognition task. Presample infusions of scopolamine significantly impaired object recognition compared with performance of the same group of rats on saline trials; this result is consistent with previous reports supporting a role for perirhinal acetylcholine in object information acquisition. Scopolamine infusions directly before the retrieval stage had no discernible effect on object recognition. However, postsample infusions of scopolamine with sample-to-infusion delays of up to 20 h significantly facilitated performance relative to postsample saline infusion trials. Additional analysis suggested that the infusion episode could cause retroactive or proactive interference with the sample object trace and that scopolamine blocked the acquisition of this interfering information, thereby facilitating recognition memory. This is, to our knowledge, the first example of improved recognition memory after administration of scopolamine. The overall pattern of results is inconsistent with a direct role for cortical acetylcholine in declarative memory consolidation or retrieval. Rather, the cholinergic input to the perirhinal cortex may facilitate acquisition by enhancing the cortical processing of incoming stimulus information.

Figure 1.

Schematic representation of the infusion protocols for each of the five experiments in the present study. The sample and choice phases are illustrated for each experiment (Exp.), and the vertical arrows indicate the various infusion times. In each experiment, a given object-recognition trial consisted of a sample phase in which the rat explored two identical objects, a 24 h retention delay, and a choice phase in which the rat was presented with a novel object and a triplicate copy of the sample object. Each vertical arrow indicates a group or condition in which saline and scopolamine were administered in counterbalanced manner over several trials in a given experiment. For experiments 4 and 5, a vertical arrow with an X represents the no-infusion condition, which was compared with the effects of immediate postsample or 3 h presample infusions of saline and scopolamine. The separation of time points in the figure is not to scale.

Figure 2.

Cannulation of rat PRh. Schematic representation of the infusion needle tip placements from a typical group of animals (experiment 1; presample group; n = 10). These placements are representative of needle tip locations in all animals included in the behavioral analyses of the present study. Cannulas were consistently located between 5.80 and 6.30 mm posterior to bregma. Some needle tips overlap in the figure.

Figure 3.

Spontaneous object recognition performance by animals in experiment 1 on trials in which they received bilateral intra-PRh infusions of scopolamine (Scop) or saline 15 min before the sample phase (presample), immediately after the sample phase (postsample), or 15 min before the choice phase (prechoice). The retention delay was 24 h. Presample intra-PRh infusions of scopolamine disrupted object recognition, but postsample infusions facilitated memory relative to saline trials. Prechoice group performance did not differ between scopolamine and saline trials. Data are presented as average discrimination ratio ± SEM. *p < 0.05.

Figure 4.

Spontaneous object recognition performance of the immediate, 20 min, and 40 min postsample infusion groups in experiment 2 on trials in which they received either saline or scopolamine (Scop) infusions bilaterally into PRh. The retention delay was 24 h. Scopolamine had an overall facilitating effect on object recognition memory. Data are presented as average discrimination ratio ± SEM.

Figure 5.

Spontaneous object recognition performance of the immediate, 8, 16, and 20 h postsample infusion groups in experiment 3 on trials in which they received either saline or scopolamine (Scop) infusions bilaterally into PRh. The retention delay was 24 h. As in experiment 2, scopolamine had an overall facilitating effect on object recognition memory when infused after the sample phase. Data are presented as average discrimination ratio ± SEM.

Figure 6.

Spontaneous object recognition performance of rats in experiment 4 on trials in which they received intra-PRh saline, intra-PRh scopolamine (Scop), or no infusion immediately after the sample phase. The retention delay was 24 h. Object recognition on saline trials was disrupted compared with memory performance in the scopolamine and no-infusion conditions. Data are presented as average discrimination ratio ± SEM. ***p < 0.001, saline versus scopolamine and saline versus no infusion.

Figure 7.

Spontaneous object recognition performance of rats in experiment 5 on trials in which they received intra-PRh saline, intra-PRh scopolamine (Scop), or no infusion 3 h before the sample phase. The retention delay was 24 h. Object recognition on saline trials was disrupted compared with memory performance in the scopolamine and no-infusion conditions. Data are presented as average discrimination ratio ± SEM. **p < 0.01, saline versus scopolamine and saline versus no infusion.