EFFECTS OF ELEVATED LEVELS OF NERVE GROWTH-FACTOR ON THE SEPTOHIPPOCAMPAL SYSTEM IN TRANSGENIC MICE

Elevating target-derived levels of nerve growth factor (NGF) in periph eral organs of postnatal mammals is known to enhance the survival of p ostganglionic sympathetic neurons and to promote the terminal arboriza tion of sympathetic axons within such NGF-rich target tissues. Althoug h increasing levels of NGF in the central nervous system can ameliorat e cholinergic function of damaged and aged neurons of the medial septu m, it remains undetermined whether the postnatal development of this n euronal population and their projections that innervate the hippocampu s are likewise affected by elevated levels of target-derived NGF. To a ddress this question, the cholinergic septohippocampal pathway was exa mined in adult transgenic mice which display elevated levels of NGF pr otein production in the dorsal hippocampus during postnatal developmen t. Adult transgenic mice possessed a cholinergic population of septal neurons approximate to 15% larger than that seen in age-matched contro l animals. Despite increased numbers of cholinergic septal neurons, as well as elevated levels of hippocampal NGF, the density of cholinergi c septal axons in the outer molecular layer of the hippocampal dentate gyrus of adult transgenic animals was comparable with that found in w ild-type controls. These results reveal that elevating levels of targe t-derived NGF during postnatal development can increase the population size of the cholinergic septal neurons but does not alter their patte rn of afferent innervation in the hippocampus of adult mice.