Bidirectional modulation of basal forebrain N-methyl-D-aspartate receptor function differentially affects visual attention but not visual discrimination performance.

Abstract

Basal forebrain neuronal circuits, specifically the corticopetal cholinergic system, mediate attentional abilities. The effects of infusions of N-methyl-D-aspartate (NMDA) and the competitive NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (APV) into the basal forebrain were assessed in rats trained in an operant task designed to generate measures of sustained attention performance. Control animals were trained in a cued visual discrimination task devoid of explicit demands on attentional performance, but involving similar basic operant components as the sustained attention task. The effects of intrabasalis infusions of NMDA (1, 3 and 6nmol) and APV (3, 10 and 20nmol) were tested in separate groups of animals. Infusion of neither drug affected the animals' response accuracy in the cued visual discrimination task, indicating that performance in this task remains insufficient to activate basal forebrain NMDA receptors. Infusions of APV in sustained attention task-performing animals selectively decreased the animals' ability to detect visual signals, but spared their ability to reject non-signal events. Conversely, infusions of NMDA into the basal forebrain did not affect the animals' hit rate but increased their number of false alarms, i.e. "claims" for signals in non-signal trials. The concentrations of NMDA infused into the basal forebrain did not result in neurotoxic effects as demonstrated by a separate experiment, which indicated neurodegeneration following the infusion of 30 nmol NMDA as visualized by the Fluoro-Jade method.The effects of APV correspond with the attentional consequences of other manipulations known to impair the functions of cortical cholinergic input. Conversely, the effects of NMDA infusions agree with the hypothesis that overactivity of cortical cholinergic inputs mediates an abnormal overprocessing of the stimulus situation. Basal forebrain NMDA receptor manipulations assist in determining the role of this neuronal system in cognitive processes.