Central muscarinic cholinergic involvement in serial pattern learning: Atropine impairs acquisition and retention in a serial multiple choice (SMC) task in rats

• Atropine impaired serial pattern acquisition and performance.
• Impairments were dependent on using associative cues.
• Atropine dissociated two different types of discriminative cue learning.
• Atropine spared rule-based serial pattern acquisition and performance.

Atropine sulfate is a muscarinic cholinergic antagonist which impairs acquisition and retention performance on a variety of cognitive tasks. The present study examined the effects of atropine on acquisition and retention of a highly-structured serial pattern in a serial multiple choice (SMC) task. Rats were given daily intraperitoneal injections of either saline or atropine sulfate (50 mg/kg) and trained in an octagonal operant chamber equipped with a lever on each wall. They learned to press the levers in a particular order (the serial pattern) for brain-stimulation reward in a discrete-trial procedure with correction. The two groups learned a pattern composed of eight 3-element chunks ending with a violation element: 123–234–345–456–567–678–781–818 where the digits represent the clock-wise positions of levers in the chamber, dashes indicate 3-s pauses, and other intertrial intervals were 1 s. Central muscarinic cholinergic blockade by atropine caused profound impairments during acquisition, specifically in the encoding of chunk-boundary elements (the first element of chunks) and the violation element of the pattern, but had a significant but negligible effect on the encoding of within-chunk elements relative to saline-injected rats. These effects persisted when atropine was removed, and similar impairments were also observed in retention performance. The results indicate that intact central muscarinic cholinergic systems are necessary for learning and producing appropriate responses at places in sequences where pattern structure changes. The results also provide further evidence that multiple cognitive systems are recruited to learn and perform within-chunk, chunk-boundary, and violation elements of a serial pattern.