GABAergic control of basal forebrain cholinergic neurons and memory

The involvement of the GABAergic innervation of basal forebrain neurons in the rats' conditional visual discrimination performance was examined. Performance in such a task is based on the subjects's ability to retrieve information about response rules, and previous experiments have demonstrated that basal forebrain lesions interfere with this ability. Following the acquisition of the task, chronic guide cannulae were stereotaxically implanted into the substantia innominata of both hemispheres, and the animals were retrained. Administration of the GABAA-agonist muscimol into the substantia innominata (0, 25, 50 ng/0.5 microliters/hemisphere) dose-dependently decreased the number of correct responses, increased the number of errors of omission, increased response latency, but did not affect side bias. Systemic co-administration of the cholinesterase inhibitor physostigmine (0, 0.1, 0.2 mg/kg; i.p.) exclusively interacted with the effects of muscimol on correct responding. Specifically, physostigmine dose-dependently intensified and attenuated the muscimol-induced reduction in correct responding. Although it cannot be excluded that alternative neuronal mechanisms were involved in the mediation of the effects of muscimol and their interaction with physostigmine, these findings support previous evidence indicating that the activity of basal forebrain cholinergic neurons is controlled by a GABAergic input, and that this neuronal link is involved in mnemonic processing.