Effects of exogenous nerve growth factor upon sympathetic sprouting into the hippocampal formation

Following septal denervation of the hippocampal formation, sympathetic fibers from a transplanted superior cervical ganglion will innervate hippocampal tissue in a topographically restricted manner. Previously, we have shown a strong correlation between the regions innervated by the sprouting sympathetic axons and the distribution of NGF immunoreactivity in the hippocampal formation, suggesting that a restricted availability of NGF trophic support may regulate the topography of innervation by the NGF-sensitive sympathetic fibers. It was possible, however, that other molecular cues were responsible for restricting neurite outgrowth to selected hippocampal regions. In the current investigation, this idea was explored by experimentally altering the distribution of hippocampal NGF using a continuous intraparenchymal infusion device. Our results indicate that some hippocampal regions, not innervated by sympathetic fibers in control animals, do become occupied when the necessary trophic factor is provided, suggesting that these regions already contained an appropriate substratum for sympathetic neurite outgrowth but lacked the necessary trophic stimulus. Other regions, however, did not become innervated even though infused NGF was verifiably present in them. Together, these findings propose that a spatial restriction of NGF may be a crucial molecular mechanism for controlling the distribution of sprouting NGF-sensitive sympathetic fibers but that other endogenous signals may regulate NGF's ability to stimulate local terminal sprouting. The data are also consistent with the idea that a limited availability of endogenous NGF is regulating both the density of sympathetic innervation into the hippocampal formation and the extent of neuronal survival within the transplanted ganglion.