THE EFFECTS OF INTRAHIPPOCAMPAL RAPHE AND OR SEPTAL GRAFTS IN RATS WITH FIMBRIA-FORNIX LESIONS DEPEND ON THE ORIGIN OF THE GRAFTED TISSUE AND THE BEHAVIORAL TASK USED/

Long-Evans female rats sustained electrolytic lesions of the fimbria a nd the dorsal fornix and, two weeks later, received intrahippocampal s uspension grafts of fetal tissue. The grafts were prepared from region s including either the medial septum and the diagonal band of Broca (s eptal grafts), or the mesencephalic raphe (raphe grafts), or from both these regions together (co-grafts). All rats were submitted to a seri es of behavioural tests (home cage and open-field locomotion, spontane ous alternation, radial-arm maze and Morris water maze performance) ru n over two periods after grafting (one to nine weeks and 20-35 weeks). Two weeks after completion of behavioural testing, histological (acet ylcholinesterase and Cresyl Violet staining) and/or neurochemical (cho line acetyltransferase activity, high-affinity synaptosomal uptake of choline and serotonin, noradrenaline, serotonin and 5-hydroxyindolacet ic acid concentrations) verifications were performed on the hippocampu s. Compared to sham-operated rats, lesion-only rats exhibited hyperact ivity which was transient in a familiar environment (home cage) and la sting in an unfamiliar one (open field), decreased rates of spontaneou s T-maze alternation, and impaired memory performance in both the radi al-arm maze and the Morris water maze. These rats also showed decrease d cholinergic and serotonergic markers with a maximal depletion in the septal two-thirds of the hippocampus. Noradrenaline concentration ten ded to be increased in the dorsal third of the hippocampus, but was no t modified in the other two-thirds. While septal grafts specifically i ncreased the cholinergic markers and raphe grafts the serotonergic one s, neither of these grafts produced a lasting effect on any behavioura l variable. Conversely, the co-grafts, which increased both the cholin ergic and serotonergic markers in the septal two-thirds of the hippoca mpus, completely normalized the Morris water maze probe trial performa nce, but failed to affect any of the other behavioural variables. Our present results confirm that grafts of fetal neurons injected into the denervated hippocampus may induce a neurochemical recovery that depen ds on the anatomical origin of the grafted cells, and that co-grafting two fetal brain regions allows the combination of their individual ne urochemical properties. Furthermore, our results show that these neuro chemical effects of the co-grafts may be involved in the recovery of b ehavioural function observed in the water maze. However, somewhat para doxically, those effects appear inefficient for inducing any recovery in other behavioural tasks, even in the radial-arm maze, which is assu med to measure similar spatial functions. Finally, it is suggested tha t the co-grafts might be more efficient in attenuating the spatial ref erence memory (Morris water maze) rather than the spatial working memo ry (radial maze) deficits subsequent to fimbria-fornix lesions.