GABAERGIC MEDIATION OF INDIRECT TRANSSYNAPTIC CONTROL OVER BASAL AND SPATIAL MEMORY TESTING-INDUCED ACTIVATION OF SEPTOHIPPOCAMPAL CHOLINERGIC ACTIVITY IN MICE

A neurochemical study of the transsynaptic interactions established between septal GABAergic interneurones and cholinergic septo-hippocampal neurones was conducted using mice. The effects of acute in vivo injections of either muscimol (20-500 ng/0.2 mul), bicuculline (100 ng- 1 mug/0.2 mul) or saline vehicle (0.2 mul) into the medial septum on septo-hippocampal cholinergic activity were evaluated using measures of hippocampal high affinity choline uptake at 30 min post-injection in two main groups of mice. The first (quiet control) remained in their home cages during the post-injection period whereas the second (active) were submitted, 10 min following injection to a 20-min period of spatial working memory testing in an 8-arm radial maze. Intraseptal injections of either muscimol or bicuculline produced significant (25-50%) inhibition of hippocampal cholinergic activity in quiet conditions (basal) as compared to intact or saline-injected mice. In the active groups, whereas memory testing induced significant cholinergic activation ( + 15-20%) in intact and saline injected mice at 30 s post-test no significant memory testing-induced activation was observed in either muscimol or bicuculline-injected mice at any dose. The role of septal GABAergic interneurones in the indirect transsynaptic control over the basal and activated states of septo-hippocampal cholinergic activity is discussed with respect to the concept that these complex neuronal interactions contribute to the physiological mechanisms involved in the modulation of working memory performance.