Use of a digital brain atlas to compare the distribution of NGF- and bFGF-protected cholinergic neurons

The effectiveness of basic fibroblast growth factor and nerve growth factor in preventing the lesion-induced disappearance of septal cholinergic neurons was compared by using a computerized data-acquisition system and a digital brain atlas that yielded quantitative and distributional information. Adult rats were given unilateral partial transections of the fimbria and then received daily intraventricular injection of one of the growth factors for 15 days. Given the high degree of co-localization of nerve growth factor receptors with choline acetyltransferase in these areas, cholinergic neurons were identified by nerve growth factor receptor immunoreactivity. Their locations were plotted in the context of a three-dimensional brain atlas permitting the analysis of relative distributions of cholinergic neurons in control brains and those of animals treated with each growth factor. The cholinergic cell disappearance induced by the partial fimbrial transection was restricted to the medial septal nucleus and the vertical limb of the diagonal band of Broca. Within the affected areas cholinergic cell disappearance increased gradually in severity from anterior to posterior levels of the septal nucleus. Both growth factors prevented the disappearance of cholinergic cell bodies in medial septal nucleus and vertical limb of the diagonal band. In lesioned control animals the unilateral cell disappearance amounted to 53.5% of the number of cholinergic neurons of the unlesioned side. Nerve growth factor and basic fibroblast growth factor reduced this disappearance to 13% and 28%, respectively. The distribution of cholinergic cells was the same in animal treated with each growth factor, suggesting that the two growth factors protect the same population of cholinergic neurons.