Induced homotypic collateral sprouting of serotonergic fibers in the hippocampus of rat.

The organization of the raphe cells efferent to the dorsal hippocampus (DHipp) has been shown to consist of two homologous groups of cells in the median raphe nucleus (MRN). Their axons project by way of the cingulum bundle (CB) and the fornix-fimbria (FF)58. A group of neurons located in the interfascicular part of the dorsal raphe nucleus (IFN) was found to use the CB route exclusively. Quantitation of the HRP-labeled cells in the MRN neurons projecting to the DHipp decreased by 55% and 92% 3 days following CB and CB-FF 5,7-DHT injections respectively. There was a significant increase in HRP-labeled neurons in the MRN at 21 and 42 days compared to 3 days after CB injection (a 2% decrease at 21 days and 38% increase at 42 days compared to sham injected). No change in the number of labeled MRN cells was seen at these long-term time points after combined CB-FF 5,7-DHT microinjections. The labeled cells in the MRN increased in size in the long survival group of CB lesioned animals. The labeled cells localized in the IFN which were lost after CB 5,7-DHT injections did not reappear after long-term survival. These results indicate that CB 5-HT fibers do not regenerate into the DHipp, but FF 5-HT fibers increase their terminal territory by collateral sprouting in response to homotypic denervation.