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Cerebral Cortex Advance Access published online on April 14, 2004
Cerebral Cortex, doi:10.1093/cercor/bhh052
© 2004 by Oxford University Press
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Article

Cortical Cholinergic Function and Deficits in Visual Attentional Performance in Rats Following 192 IgG-Saporin-induced Lesions of the Medial Prefrontal Cortex

Jeffrey W. Dalley 1*, David E. Theobald 1, Pascale Bouger 1, Yogita Chudasama 2, Rudolf N. Cardinal 1, Trevor W. Robbins 1

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

* To whom correspondence should be addressed. E-mail: jwd20{at}cus.cam.ac.uk.


  Abstract

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 rein-statement 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.

Key Words: 192 IgG-saporin, acetylcholine, five-choice serial reaction time task, impulsivity, medial prefrontal cortex, muscarinic receptors, visual attention


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