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Updated: May 22, 2026

Novel Object Recognition Test for the Investigation of Learning and Memory in Mice
Published on: August 30, 2017
Differential effects of m1 and m2 receptor antagonists in perirhinal cortex on visual recognition memory in monkeys
Wei Wu1, Richard C Saunders, Mortimer Mishkin
1Laboratory of Neuropsychology, NIMH, Bethesda, MD 20892, USA.
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.
Insights
Blockading M1 muscarinic receptors in the perirhinal cortex impairs visual recognition memory. This suggests M1 receptors are crucial for forming new visual memories, unlike M2 receptors.
Area of Science:
- Neuroscience
- Cognitive Neuroscience
- Pharmacology
Background:
- Muscarinic receptors in the perirhinal cortex are vital for recognition memory.
- Nonselective muscarinic antagonist scopolamine impairs visual recognition tasks.
Purpose of the Study:
- To investigate the specific roles of M1 and M2 muscarinic receptor subtypes in the perirhinal cortex during visual recognition memory formation.
- To determine if M1 receptor blockade is responsible for the memory deficits observed with scopolamine.
Main Methods:
- Local microinfusions of M1-selective antagonist pirenzepine or M2-selective antagonist methoctramine into the perirhinal cortex of animals.
- Performance assessment on a one-trial visual recognition task.
- Comparison of results with saline infusions and scopolamine administration.
Main Results:
- Pirenzepine infusions significantly impaired visual recognition accuracy.
- Methoctramine infusions did not significantly affect recognition accuracy.
- Scopolamine and pirenzepine produced similar memory deficits, indicating M1 receptor blockade as the primary cause.
Conclusions:
- M1 and M2 muscarinic receptors have distinct functional roles in the perirhinal cortex.
- Cholinergic activation of M1 receptors is essential for the formation of new visual memories.
- Perirhinal M1 receptors are critical for visual recognition memory.
