Modest cholinergic deafferentation fails to alter hippocampal G-proteins

The integrity of hippocampal G-protein mediated signalling following ibotenate induced lesion of the medial septum was examined. The lesion was confined 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 survival period. The relative levels of five G-protein subunits (Gbeta, G(alpha)o, G(alpha)i1, G(alpha)i2, and G(alpha)s-L), basal GTPase, the degree of carbachol- or baclofen-stimulated GTPase activities, and the basal and fluoroaluminate-stimulated adenylate cyclase activities were apparently unaffected. To determine if our assay methodology was sensitive to changes in pre-synaptic signalling, we compared G-protein density in synaptosomes with total hippocampal homogenates. The concentration of G(alpha)q/11, G(alpha)i1, and G(alpha)i2. were significantly lower in synaptosomes, while G(alpha)o, was only marginally reduced. Thus, modest lesions of the medial-septal nucleus fail to alter G-protein signalling. However, our findings that G-protein density is lower in synaptosomal membranes than in total homogenates, indicates that the analysis of signalling events in synaptosomes following deafferentation could clarify adaptive changes which may occur at the presynaptic level.