Reorganization of the area dentata serotoninergic plexus after lesions of the median raphe nucleus

Abstract

Serotoninergic projections from the dorsal and median raphe nuclei to the area dentata of the hippocampal formation terminate mainly in the molecular layer and hilus, respectively. Consequently, a reduction in the density of the hilar serotoninergic plexus is seen by immunocytochemistry 2 weeks after lesions of the median raphe nucleus. Hippocampal serotonin concentration and serotonin high affinity uptake are also significantly reduced. Six weeks after lesion, surviving serotoninergic axons form a dense band in the inner molecular layer of the dorsal area dentata, a region that usually contains a sparse serotoninergic plexus. Moreover, serotoninergic fibers traverse the molecular layer and pass through the granule cell layer to reinnervate the hilus. Serotonin concentration and high affinity uptake have recovered to near normal levels by 6 weeks postlesion. Changes in the anatomical distribution of the area dentata serotoninergic plexus have not been reported in cases in which serotoninergic sprouting follows axotomy of serotoninergic projections. Thus direct lesions of serotoninergic neurons can produce a homotypic compensatory response that is qualitatively different from that generated by axotomy. The mechanistic basis for this reorganization is unclear, but the apparent extension of serotoninergic axon collaterals toward the hilus suggests that the denervated hilar neuropil is guiding reinnervation. Finally, anatomical evidence from animals studied 10 weeks postlesion suggests that the compensatory proliferation of serotoninergic axons observed 6 weeks after median raphe lesion is a transient event.