Cerebral Cortex Advance Access originally published online on April 14, 2004
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Cerebral Cortex August 2004; 14:922-932
© Oxford University Press 2004
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Cortical Cholinergic Function and Deficits in Visual Attentional Performance in Rats Following 192 IgG–Saporin-induced Lesions of the Medial Prefrontal Cortex
1 Department of Experimental Psychology, University of Cambridge, Downing St., Cambridge CB2 3EB, UK, 2 NIH/NIMH, Laboratory of Neuropsychology, 49 Convent Drive, Besthesda MD 20892-4415, USA
Lesions of the basal forebrain (BF) cortical cholinergic system impair performance on a rodent five-choice visual attentional task. This study examines the effects on the same task of selective depletion of acetylcholine from the prefrontal cortex (PFC) using 192 IgG–saporin, the cholinergic immunotoxin. Rats were trained to detect brief visual stimuli, either presented unpredictably both temporally and spatially to increase attentional load, or under less demanding conditions where stimuli were temporally and spatially predictable. Following training, 192 IgG–saporin (50 ng or 100 ng/infusion) or its vehicle was infused bilaterally into the ventromedial PFC. The 100 ng lesion group exhibited post-operatively a transient increase in perseveration, specifically when the visual stimuli were temporally unpredictable. A vigilance decrement, as well as a reinstatement of perseverative responding occurred in both lesion groups under conditions of enhanced attentional load, specifically with high target frequency sustained over many trials. Lesioned subjects were also more impulsive with increased anticipatory errors. Systemic administration of the muscarinic receptor antagonist scopolamine further dissociated the groups with attentional accuracy in the 100 ng group decreasing relative to shams. These findings are consistent with an important modulatory influence of PFC function by BF cholinergic neurons, particularly during increased attentional demand.
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