Critical role of the cholinergic system for object-in-place associative recognition memory

Abstract

Object-in-place memory, which relies on the formation of associations between an object and the place in which it was encountered, depends upon a neural circuit comprising the perirhinal (PRH) and medial prefrontal (mPFC) cortices. This study examined the contribution of muscarinic cholinergic neurotransmission within this circuit to such object-in-place associative memory. Intracerebral administration of scopolamine in the PRH or mPFC impaired memory acquisition, but not retrieval and importantly we showed that unilateral blockade of muscarinic receptors simultaneously in both regions in opposite hemispheres, significantly impaired performance. Thus, object-in-place associative memory depends upon cholinergic modulation of neurones within the PRH-PFC circuit.

Figure 1.

Diagrammatic representations of the individual infusion sites in each animal. (A) Bilateral medial prefrontal (mPFC) group. (B) Bilateral perirhinal (PRH) group. (C) The mPFC infusion sites of the PRH+mPFC group. (D) The PRH infusion sites of the PRH+mPFC group. All of the infusion sites were within the PRH or mPFC.

Figure 2.

Discrimination between the objects was calculated using a discrimination ratio, which takes into account individual differences in the total amount of exploration. The discrimination ratio is calculated as follows: the difference in time spent by each animal exploring objects that changed position compared to the objects that remained in the same position divided by the total time spent exploring all objects. (A) Infusion of scopolamine (Scop) into the perirhinal cortex (PRH) significantly impaired performance in the object-in-place task following a 5 min and a 1 h delay. (B) Infusion of scopolamine (Scop) into the medial prefrontal cortex (mPFC) significantly impaired performance in the object-in-place task following a 5 min and a 1 h delay. Illustrated for each group is the mean (+ SEM) discrimination ratio. * P < 0.05; ** P < 0.01; and *** P < 0.001 difference between groups.

Figure 3.

Unilateral scopolamine infusions into the PRH and mPFC in opposite hemispheres (Scop Contra) impaired object-in-place performance following both a 5 min and a 1 h delay. Scopolamine infusions into both the PRH and mPFC in the same hemisphere (Scop Ipsi) had no effect on performance following either delay. ** P < 0.01 and *** P < 0.001 difference between groups.