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Abstract

The nervous system is adaptive, so that its neuronal properties can be modified by learning to respond to new categories of stimuli. This is a crucial function of the nervous system not only in children but also in adults and its malfunction can lead to a severely disabling mental disease known as Alzheimer's or senile dementia. Acetylcholine (ACh) is one of the modulators implicated in the brain's adaptive behaviour. Indeed ACh plays an important role in many cognitive functions, including attention (Sarter and Bruno, 2000 Neuroscience 95 933 - 952; Furey et al, 2008 Neuropsychopharmacology 33 913 - 923; Herrero et al, 2008 Nature 454 1110 - 1114), cue detection (Parikh and Sarter, 2008 Annals of the New York Academy of Sciences 1129 225 - 235), learning (Sarter et al, 2003 Neurobiology of Learning Memory 80 245 - 256), short term-memory (Miller and Desimone, 1993 Neuroreport 4 81 - 84; Thomas et al, 1999 Neuropsychologia 46 2476 - 2484), and long-term memory retrieval (Sarter et al, 2003 Neurobiology of Learning Memory 80 245 - 256; Rosier et al, 1999 European Journal of Neuroscience 11 3701 - 3714), as well as in Alzheimer's disease. We have examined the effects of scopolamine--an antagonist of muscarinic ACh receptors--on object recognition in macaques. The animal was taught a categorization task, ie to classify stimuli to categories by appropriate behavioural responses. The paradigm involved a fixation task during which an image that belonged to one of the categories was presented. The macaque used levers to categorize the stimulus. Performance of this task was disrupted following injections of scopolamine. When presented with stimuli that belonged to one of these categories but had not been seen before, scopolamine significantly impaired performance in the categorization task. The monkey was still able to carry out the task with a set of familiar stimuli, ie stimuli that it had previously categorized successfully. Performance deteriorated as the stimulus became less salient by increasing the level of visual noise. Scopolamine, however, had no significant or long-lasting effect on performance with familiar stimuli at the different noise levels. In our attempt to localize the effects of ACh we used an analogue of scopolamine that cannot cross the blood brain barrier. The analogue (butyl scopolamine) mimicked the peripheral actions of scopolamine but caused no cognitive deficit. The cognitive changes, therefore, reflect ACh's effect in the brain. The exact site of the effect has not yet been established but is likely to depend on forebrain mechanisms.