FIMBRIA-FORNIX LESIONS IMPAIR SPATIAL PERFORMANCE AND INDUCE EPILEPTIC-LIKE ACTIVITY BUT DO NOT AFFECT LONG-TERM POTENTIATION IN THE CA1 REGION OF RAT HIPPOCAMPAL SLICES

Groups of rats were given bilateral fimbria-fornix lesions and one month later grafted into the hippocampus with fetal cholinergic and non-cholinergic (hippocampal) neural tissue. Three weeks and 3 months after transplantation the animals were trained to find and then to retain the location of a hidden platform in the Morris water maze. After the final behavioral testing phase, electrophysiological studies of the short- and long-term potentiation (STP and LTP) and epileptiform activity of evoked responses were performed in vitro in the CA1 region of the hippocampus. The lesions produced a marked deficit in spatial function in the early testing phase which showed some recovery at the three month time point. Neither the cholinergic nor the non-cholinergic grafts improved spatial performance; indeed, on some measures these groups showed a significantly greater deficit than the lesion-alone group, Epileptiform activity, which was defined as the ratio of the sum of amplitudes of second and third population spikes to the amplitude of the first, before tetanization was not significantly different for all groups. After tetanization of the radiatum input, however, the epileptiform activity in the FFL group was significantly higher in comparison to that of the control groups. Grafting of cholinergic tissue decreased this parameter to the control level, but non-cholinergic grafts did not modify the lesion-induced epileptiform activity. Epileptiform activity after tetanization of the oriens input was approximately equal for all groups. There were no significant differences between surgical groups in TP and LTP for both the oriens and radiatum inputs. The results suggest that, when measured in vitro, epileptiform activity rather than long-term potentiation in CA1 is associated with loss of cognitive function in vivo following deafferentation of the hippocampus.