Modest cholinergic deafferentation fails to alter hippocampal G-proteins

The integrity of hippocampal G-protein mediated signalling following iboten ate induced lesion of the medial septum was examined. The lesion was confin ed histologically to the septum and induced a 23% reduction in hippocampal choline acetyltransferase (ChAT) activity and G-proteins levels and related enzyme activities were measured in the hippocampus following a 21 day surv ival period. The relative levels of five G-protein subunits (G(beta), G(alp ha o), G(alpha i1), G(alpha i2), and G(alpha s-L)), basal GTPase, the degre e of carbachol- or baclofen-stimulated GTPase activities, and the basal and fluoroaluminate-stimulated adenylate cyclase activities were apparently un affected. To determine if our assay methodology was sensitive to changes in pre-synaptic signalling, we compared G-protein density in synaptosomes wit h total hippocampal homogenates. The concentration of G(alpha q/11), G(alph a i1), and G(alpha i2), were significantly lower in synaptosomes, while G(a lpha o), was only marginally reduced. Thus, modest lesions of the medial-septal nucleus fail to alter G-protein s ignalling. However, our findings that G-protein density is lower in synapto somal membranes than in total homogenates, indicates that the analysis of s ignalling events in synaptosomes following deafferentation could clarify ad aptive changes which may occur at the presynaptic level. (C) 1999 Elsevier Science Ltd. All rights reserved.