Baxter MG, Kyriazis DA, Croxson PL (2008) Cholinergic depletion of prefrontal cortex impairs acquisition of the delayed response task in rhesus monkeys. Neuroscience 2008 Abstracts 292.9/SS22. Society for Neuroscience, Washington, DC.
Summary: The involvement of corticopetal cholinergic projections in cognition remains difficult to define. Some investigators have suggested that normal cortical function requires an intact cholinergic input, whereas others emphasize a selective role of acetylcholine in attentional function or plasticity. Because of the anatomical and functional homology of human and macaque cortical structures, studies of the effects of selective ablation of cholinergic projections to cortical regions in the macaque would clarify the functions for which these projections are essential. We have tested 3 male rhesus monkeys with multiple bilateral injections of the immunotoxin ME20.4-saporin into lateral and orbital prefrontal cortex on a suite of cognitive tasks dependent on the integrity of orbital and ventrolateral prefrontal cortex, on which they were unimpaired. These tasks included new object-in-place scene learning, strategy implementation, and reinforcer devaluation. To determine the involvement of acetylcholine in dorsolateral prefrontal cortex function, we then trained these monkeys on the spatial delayed response task (Goldman, 1970; Bachevalier and Mishkin, 1986) in a manual testing apparatus. In this task the monkey watches as an experimenter places a small food reward in one of two wells of a test tray and then covers both wells with identical gray plaques. After a brief delay (1-5 sec) during which an opaque screen is interposed between the monkey and experimenter, the monkey is allowed to obtain the reward by displacing the plaque covering the well that was baited by the experimenter. Thus, the monkey must maintain the baited location (left or right) in memory during the brief delay interval in order to choose correctly. Performance of this task is devastated by ablation of dorsolateral prefrontal cortex. The monkeys with cholinergic depletion of lateral and orbital prefrontal cortex were also unable to learn the task to criterion, which four unoperated control monkeys learned readily. This finding suggests that acetylcholine, although not critical for functions of ventrolateral and orbital prefrontal cortex, is essential for dorsolateral prefrontal cortex function. An alternative explanation, which we are currently investigating, is that acetylcholine is necessary for the prefrontal cortex to adapt to the different task demands of delayed response, relative to the tests of discrimination learning with which these monkeys had extensive experience. This would be consistent with a role for cholinergic input to neocortex in cortical plasticity and remodeling.
Related Products: ME20.4-SAP (Cat. #IT-15)