Differential effects of m1 and m2 receptor antagonists in perirhinal cortex on visual recognition memory in monkeys

Abstract

Microinfusions of the nonselective muscarinic antagonist scopolamine into perirhinal cortex impairs performance on visual recognition tasks, indicating that muscarinic receptors in this region play a pivotal role in recognition memory. To assess the mnemonic effects of selective blockade in perirhinal cortex of muscarinic receptor subtypes, we locally infused either the m1-selective antagonist pirenzepine or the m2-selective antagonist methoctramine in animals performing one-trial visual recognition, and compared these scores with those following infusions of equivalent volumes of saline. Compared to these control infusions, injections of pirenzepine, but not of methoctramine, significantly impaired recognition accuracy. Further, similar doses of scopolamine and pirenzepine yielded similar deficits, suggesting that the deficits obtained earlier with scopolamine were due mainly, if not exclusively, to blockade of m1 receptors. The present findings indicate that m1 and m2 receptors have functionally dissociable roles, and that the formation of new visual memories is critically dependent on the cholinergic activation of m1 receptors located on perirhinal cells.

Figure 1

MRI-guided targeting of the monkey’s perirhinal cortex. Upper panel: MR image of a coronal brain section showing (i) bilateral tracks left by guide tubes through which the injection cannulae were lowered and (ii) bilateral infusions of the MR contrast agent gadolinium (white areas). The cap-shaped object above the brain is postoperative granular-tissue growth between the dura mater and the guide-grid chamber (the latter being invisible to MR in this image taken after the gadolinium was removed from the chamber). Lower panels: Enlarged views of the ventral part of the section shown in the upper panel. Yellow lines outline the brain’s pial surface, and green lines, the border between grey and white matter. As shown in these views, the infusions were limited largely to the perirhinal cortex, located in the lateral half of the inferior temporal gyrus (i.e. the gyrus between tma and rh). Abbreviations: 28, Brodmann area (BA) 28 or entorhinal cortex; 35, BA 35 or perirhinal cortex in the lateral bank of the rhinal sulcus; 36, BA 36 or perirhinal cortex on the gyral surface; Amyg, amygdala; rh, rhinal sulcus; tma, anterior middle temporal sulcus; ts, superior temporal sulcus.

Figure 2

DNMS performance. Percent errors above the mean noninjection baseline score after bilateral perirhinal infusions of saline and the indicated drug concentrations in millimolar (mM). Abbreviations: MET, methoctramine; PIR, pirenzepine; SAL, saline; SCOP, scopolamine.