Acetylcholine release from visual and sensorimotor cortices of conditioned rabbits: the effects of sensory cuing and patterns of responding.

A technique was devised for the collection of acetylcholine (ACh) released from the cerebral cortex of awake rabbits while they were performing a previously learned operant task. Based on the assumption that ACh release is directly proportional to the activity of cholinergic synapses under the area of collection, two hypotheses of the functional role of cortical cholinergic mechanisms were examined: (1) that activity in cholinergic neurons is related to the inhibition of responding; (2) that cholinergic activity is related to the perception of a 'significant' stimulus. Five groups trained on different behavioral paradigms were used to test these hypotheses. ACh release was collected concurrently from visual and sensorimotor cortices to differentiate diffuse from specific cortical effects. A small (50-100%) increase in ACh release was found in all groups and from both cortical areas. In the case of one group (visually cued, reinforced for low response rates) a significantly greater increase occurred from sensorimotor cortex only. These findings do not support either hypothesis alone, and are interpreted as evidence for two cholinergic systems within, or projecting to the cortex. One is related to generalized behavioral arousal and desynchronization of the electroencephalogram. Activation of the second cholinergic system is dependent on both response inhibition and the presence of a significant stimulus of the visual (but not of the auditory) modality.