Long-lasting cholinergic modulation underlies rule learning in rats

We studied the role of acetylcholine (ACh) in creating learning-related lon g-lasting modifications in the rat cortex. Rats were trained to discriminat e positive and negative cues in pairs of odors, until they demonstrated rul e learning and entered a mode of high capability for learning of additional odors. We have previously reported that pyramidal neurons in olfactory (pi riform) cortex from trained rats had reduced spike afterhyperpolarization ( AHP) for 3 d after rule learning. In the present study we examined the mech anism underlying this long-lasting modification. The cholinergic agonist ca rbachol reduced both slow AHP and firing adaptation in neurons from pseudot rained rats, but had no effect on neurons from trained rats, suggesting pre -existing cholinergic effect. Intracellular application of the calcium chel ator BAPTA abolished the difference in slow AHP and in adaptation between g roups, suggesting that the difference resulted from reduction in the ACh-se nsitive, Ca2+-dependent potassium current, I-AHP. At the behavioral level, application of the muscarinic blocker scopolamine before each training sess ion delayed rule learning but had no effect on further acquisition of odor memory. We suggest that intense ACh activity during rule learning enhances neuronal excitability in the piriform cortex by reducing I-AHP and that the effect outlasts the stage of rule learning, so that ACh activity is not cr ucial for further odor learning.