Muscimol injections into the nucleus basalis magnocellularis of rats: selective impairment of working memory in the double Y-maze

Abstract

Anatomical and neurochemical results suggest that the cortico- and amygdalopetal cholinergic neurons of the nucleus basalis magnocellularis (NBM) may receive GABAergic inputs. The present experiments were undertaken to evaluate the possible influence of intra-NBM injections of the GABA A agonist, muscimol, on memory. In two experiments, rats were chronically implanted with guide cannulae placed bilaterally into the NBM. Rats were trained to a criterion of at least 83% correct on each component in a double Y-maze task that allowed a dissociation of working and reference memory. The task began with placement into one of the two end arms of the first Y-maze and the reference memory task was to go to the stem for food. Access to the second Y was then given and the working memory task was to go to the goal arm opposite the arm in the first maze from which that trial began. In experiment 1, pre-trained rats ( n = 7) received muscimol (0.5 μl) in doses of 0, 0.01, 0.1 and 1.0 μg in a counterbalanced order with re-training to criterion between injections. In experiment 2, pre-trained rats ( n = 8) received saline, muscimol (0.1 μg), the GABA A antagonist, bicuculline (0.01 μg), and muscimol + bicuculline. Results of experiment 1 revealed that intra-NBM muscimol produced a dose-dependent and differential impairment of working and reference memory. A dose of 0.1 μg impaired working memory without significantly affecting reference memory; doses of 0.01 μg and 1.0 μg affected neither and both types of memory, respectively. In experiment 2, the differential mnemonic effect of 0.1 μg muscimol was replicated and co-injection with bicuculline significantly reduced this effect. Results suggest that GABA in the NBM may modulate memory, possibly by influencing cholinergic cells there.