Septohippocampal cholinergic changes after destruction of the A10-septal dopaminergic pathways

Mice were injected bilaterally into the septum with 6-hydroxydopamine and 6 weeks later the hippocampi were assayed for activity of choline acetyltransferase, muscarinic receptor binding capabilities and for formation of inositol phosphate in response to direct (carbachol) or presynaptically elicited (K⁺) stimulation of the postsynaptic receptors. Levels of dopamine in the septum were reduced by 70% in the lesioned animals and hippocampal choline acetyltranferase was elevated by the same amount. The B_max of muscarinic binding was significantly reduced without changes in K_d; nevertheless, carbachol-induced stimulation of formation of inositol phosphate was unaffected. The response of K⁺ was markedly elevated in the 6-hydroxydopamine-treated animals. Thus, the regulatory effect of A10-septal dopaminergic pathways on the septohippocampal cholinergic innervations is both on the presynaptic and postsynaptic levels.