A role for acetylcholine in conditioning-related responses of rat frontal cortex neurons: microiontophoretic evidence

In an associative conditioning paradigm, an auditory stimulus (CS+) was paired with rewarding medial forebrain bundle stimulation or a tone of different frequency (CS-) was presented without pairing. After training, slow potential (SP) and single neuron responses were recorded from rat frontal cortex. When cortical SP responses indicated the development of discrimination between CS+ and CS- tones, single neurons could be isolated that exhibited a discriminative response to CS+. Seventy-three percent of the 56 neurons which discriminated between CS+ and CS- were excited by the paired tone while the remainder were inhibited. Iontophoretically applied acetylcholine increased spontaneous firing rate in 90% of the excited cells and 87% of the inhibited cells. Iontophoretic administration of a muscarinic receptor antagonist, either atropine or tropicamide, during trial presentation attenuated the conditioning-related response to CS+ as well as the response to acetylcholine in the majority of neurons. The largest group of discriminating neurons were excited by both CS+ and acetylcholine, and both responses were suppressed by the antagonists. The results provide evidence that conditioning-related responses of a major population of frontal cortex neurons are modulated by cholinergic input, a portion of which may originate in the basal forebrain area. There also may be a significant non-cholinergic influence on these neuronal responses.