Raphe grafts in the hippocampus, but not in the entorhinal cortex, reverse hippocampal hyperexcitability of serotonin-depleted rats and restore their responsiveness to fenfluramine

We compared the effects of embryonic raphe grafted into either the hippocampus or the entorhinal cortex, on the responsiveness of dentate granule cells to stimulation of the perforant path. Raphe grafts in the hippocampus reversed the hyperexcitability of granule cells, resulting from depletion of the serotonergic innervation. Such grafts also restored the responsiveness of the granule cells to application of a serotonin releasing drug, fenfluramine (FFA). In contrast, hyperexcitability was not reversed when the graft was placed in the entorhinal cortex. Furthermore, although some increase in population spike size was observed in these rats after application of FFA, this increase had a response profile which was different from that of control and of lesioned rats that were grafted in the hippocampus. These results suggest that the serotonergic innervation, within the hippocampus and not in the entorhinal cortex, modulates granule cells excitability.