Nerve growth factor but not neurotrophin-3 is synthesized by hippocampal gabaergic neurons that project to the medial septum

Conventional uptake of neurotrophins takes place at axon terminals via spec ific receptors, and is followed by retrograde transport. Recent studies dem onstrated that, with the exception of nerve growth factor, other neurotroph ins may be delivered anterogradely to the region containing the receptor ex pressing neurons. In this study we used a triple labeling method that combi nes retrograde tract tracing, in situ hybridization and immunocytochemistry to examine whether non-principal cells projecting from the hippocampus to the septum synthesize nerve growth factor. Our results show that, on averag e, 59% of the horseradish peroxidase-labeled hippocamposeptal nonpyramidal neurons also display nerve growth factor messenger RNA hybridization signal . The ratio was slightly higher in the CAI stratum oriens and the hilus of the dentate gyrus (64 and 62%, respectively) compared to stratum oriens of the CA3 region (58%), In addition, we demonstrated that many nerve growth f actor-positive septally projecting neurons also contain the calcium-binding protein calbindin D-28K, whereas nerve growth factor-negative projecting c ells mostly lack this neurochemical marker. In contrast to nerve growth fac tor, neurotrophin-3 has never been found in hippocamposeptal cells. Hippocamposeptal GABAergic cells are reciprocally connected with the medial septum, thus they are in a key position to regulate nerve growth factor re lease as a function of the activity level in the septohippocampal system. F urthermore, our results raise the intriguing possibility that nerve growth factor may be transported also in an anterograde manner. Regardless of the direction of transport, the presence of nerve growth factor in hippocampose ptal cells suggests that long distance fast synaptic mechanisms and slow ne urotrophin action are coupled in these neurons. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.