Brain Research 200 (1980) 259-269 259 © Elsevier/North-Holland Biomedical Press SEPTAL ELICITATION OF HIPPOCAMPAL THETA RHYTHM AFTER LOCALIZED DE-AFFERENTATION OF SEROTONINERGIC FIBERS N. McNAUGHTON, E. C. AZMITIA*, J. H. WILLIAMS, A. BUCHAN and J. A. GRAY Department of Experimental Psychology, Oxford University, Oxford and Department of Anatomy, Cambridge University, Cambridge (U.K.) (Accepted May 1st, 1980) Key words: hippocampal theta rhythm - - median raphe - - serotonin - - neurotoxlc lesions - - cingu- lum fornix SUMMARY Previous experiments using serotonin antagonists and electrolytic raphe lesions suggest that the serotonergic input to the hippocampus inhibits low frequency (<7 Hz) theta rhythm in the rat, whereas experiments using raphe stimulation suggest facilitation. The present experiments employed neurotoxic lesions of the serotonergic input to the hippocampus in an attempt to reproduce the effects of systemically administered antagonists. If the septal area is stimulated at frequencies between 6 and 10 Hz in the rat, the threshold current for driving hippocampal theta is minimum at 7.7 Hz. Systemic blockade of serotonergic synapses has been shown to shift this minimum to 6.9 Hz. In the present experiments, neurotoxic lesions were made with injections of 5,7- dihydroxytryptamine into the cingulum bundle, fornix or both. The observed effect depended on the loss of serotonin in the hippocampus, rather than the site of injection, and extensive depletion shifted the minimum to 6.9 Hz. These results indicate that the fornix and cingulum serotonergic inputs to the hippocampus are functionally homogenous, at least with respect to this response; and that the effects of systemic manipulation of serotonin systems on the septal elicitation of hippocampal theta rhythm may be attributed to changes in these two inputs. INTRODUCTION The median raphe (MR) nucleus is the source of an important serotonergic pro- jection to the hippocampusS,S,9,t4,17. These fibres enter the hippocampus by two dis- * Present address: Department of Anatomy, Mount Sinai School of Medicine, New York, N.Y. 10029, U.S.A.