Learning-Induced Changes in Muscarinic Receptor Binding Density as a Function of Cognitive Strategy
Evidence from previous studies on the multiple memory systems model suggests that specific brain regions cooperate and compete to mediate the navigational strategies used to locate a goal in a spatial environment. Specifically, the cholinergic system within these discrete brain regions plays a key role in balancing this mediation such that acetylcholine release, genomic changes, and receptor regulation at cholinergic synapses are altered following learning and subsequent memory consolidation. Based on previous findings, we proposed to test learning-induced changes in muscarinic receptor binding expression in adult male rats following training on a water maze task guided either by a cue proximal to the escape platform (stimulus-response strategy), by cues surrounding the maze (place strategy) or by alternating between the two strategies (strategy-switching). The primary findings of the current study demonstrate that adult male rats that navigated to an escape platform guided by cues surrounding a water maze (place-trained) learned the task at a significantly slower rate than males that were guided by a cue proximal to the platform (stimulus-response-trained) or males that were required to switch strategies on alternating days. Additionally, males that were required to switch strategies over alternating days expressed higher ratios of muscarinic binding in the hippocampus relative to the striatum compared to place-trained rats, stimulus-response-trained rats, and swim-only controls. These results indicate that the use of a place learning strategy slows acquisition of a water maze task while the requirement to switch strategies as the demands of the task change over days engages the cholinergic system in the hippocampus most heavily. Taken together, the results from the current study further confirm the involvement of cholinergic function in regulating the balance between multiple memory systems.