Selective cholinergic lesions in the rat nucleus basalis magnocellularis with limited damage in the medial septum specifically alter attention performance in the five-choice serial reaction time task-

Authors
H. Harati, A. Barbelivien, B. Cosquer, M. Majchrzak, J.-C. Cassel.

Lab
Laboratoire d'Imagerie et de Neurosciences Cognitives UMR 7191, Université Louis Pasteur, CNRS, Institut Fédérératif de Recherche 37 de Neurosciences, Strasbourg, France.

Journal
Neuroscience

Abstract
Selective immunotoxic cholinergic lesions in the nucleus basalis magnocellularis (NBM) impair visuospatial attention performance in a 5-choice serial reaction time task (5-CSRT task). The features of the reported deficits, however, do not perfectly match among studies, in which some lesions may have been too weak while others largely encroached onto the septal region. Using the 5-CSRT task, we therefore re-assessed the effects of NBM lesions that produced minimal septal damage. Long-Evans adult male rats were trained to stable 5-CSRT task performance (stimulus duration: 0.5 s) and subsequently subjected to intra-NBM injections of 192 IgG-saporin (200 ng/side). The lesions induced more than 90% loss of choline acetyltransferase–positive neurons in the NBM vs. only 28% in the medial septum. The decrease of the optical density of acetylcholinesterase reaction products was significant in the cortex (_91%), not in the hippocampus. In the 5-CSRT task, the lesions resulted in increased omissions (from 10% to 30%) and decreased correct responses (from 80% to 60%), with negligible or no effects on all other usually collected variables. This deficit disappeared with lengthened stimulus duration (i.e. 0.5–1 and then 5 s). Furthermore, overall performance levels decreased when the stimulus duration was shortened (i.e. 0.5–0.2 s) or its intensity attenuated, and rats with cholinergic lesions remained consistently impaired vs. controls. These results show that disruption of sustained visual attention functions by damage to the NBM cholinergic neurons can be evidenced despite weak or no effects on variables accounting for motivational, locomotion- or impulsivity-related biases. Discrepancies with previously reported results are discussed in terms of differences in lesion extent/specificity and training levels.