Selective immunolesioning of the basal forebrain cholinergic neurons in rats: effect on attention using the 5-choice serial reaction time task

Abstract

Rationale. Excitotoxic lesions of the nucleus basalis magnocellularis (nbm) in rats produce deficits in performance of the 5-choice serial reaction time (5CSRT) task, suggesting that basal forebrain cholinergic projections to the neocortex play an important role in visuospatial attention. However, non-selective damage induced by excitotoxins may have confounded the interpretation of the specific contribution of the corticopetal cholinergic neurons of the nbm to attentional processes.

Objective. The purpose of the present study was to produce selective immunolesions of the cholinergic neurons of the nbm in order to examine more precisely the role of the cholinergic projections of the basal forebrain on attentional performance in a 5CSRT task.

Methods. Rats received bilateral injections of the selective cholinergic immunotoxin 192 IgG-saporin (0.067 µg/µl, 1 µl) into the nbm after baseline training in the 5CSRT task. Performance of sham and nbm lesion groups was then assessed during baseline and increased task difficulty conditions.

Results. Contrary to results previously reported, accuracy of responding and behavioral inhibition were unaffected by the immunotoxin. Rats with nbm lesions showed, however, significant increases in omissions relative to control rats, most markedly during sessions with increased difficulty of signal detection, e.g., decreased stimulus intensity or duration. Magazine and correct latencies were unaffected, suggesting that the lesion-induced omissions were not due to changes in motivation. Omissions were highly correlated with percentage of choline acetylcholine transferase depletion. Reduced premature responses were also observed when the target stimulus was made less predictable.

Conclusions. Although the 192 IgG-saporin lesion produced a different array of behavioral deficits than previously reported, these effects nevertheless are consistent with an important role of the basal forebrain cholinergic system in attentional function, in particular with accurate timing of stimulus presentation and target detection.