[Improvement in spontaneous and acquired spatial behaviors following lesions of septal dopaminergic afferents in mice: possible relations with hippocampal cholinergic activity].

Recent evidence from pharmacological studies support the view that dopaminergic afferents to the septal complex which originate from the mesencephalic A10 area, exert a tonic inhibitory control over the activity of the septal-hippocampal cholinergic neurons. Accordingly one could predict that the release from such an inhibition by lesion of the septal dopaminergic terminals might improve performance in tasks known to be related to hippocampal cholinergic activity. In order to test this hypothesis mice of the C57BL/6 strain received a bilateral injection of 6-hydroxydopamine in the lateral septal nucleus; they were compared to subjects receiving saline and to unoperated control mice in tests performed in a T-maze: spontaneous alternation, acquisition and reversal of spatial discrimination. In all tasks, performance of experimental subjects was improved relative to controls. However, subsequent experiments showed that this improvement was not observed when visual (light/dark) discrimination was used. Finally, 6-hydroxydopamine injected mice exhibited a substantial increase in hippocampal sodium-dependent high affinity choline uptake (+ 16.7%). These results are discussed in relation to the three main theories concerning the role of the septo-hippocampal complex and cholinergic system in the control of behavior (i.e. Pavlovian internal inhibition, spatial mapping and working memory). Only the theory of spatial cognition seems to account for our present findings.