In previous experiments it has been demonstrated that the synthesis of BDNF (brain-derived neurotrophic factor) and NGF in neurons of the hippocampus is regulated by neuronal activity. The glutamate system is predominantly responsible for upregulation and the GABAergic system for downregulation both in vitro and in vivo (Zafra et al., 1990, 1991). The aim of the present study is to examine the extent to which the cholinergic system is also involved in the regulation of NGF and BDNF mRNA and whether the regulatory contribution of the cholinergic system changes during development. Partial transection of the fimbria fornix bundle in the second postnatal week resulted in a reduction of BDNF and NGF mRNA levels in the hippocampus, suggesting that septal cholinergic input is involved in the regulation of hippocampal BDNF and NGF mRNA levels. Because the fimbria fornix bundle also contains fibers other than cholinergic ones, we further evaluated the importance of the cholinergic influence by injecting pilocarpine, a muscarinic agonist. Pilocarpine markedly increased hippocampal BDNF and NGF mRNA levels in both early postnatal and adult rats. In situ hybridization experiments demonstrated that pilocarpine led to an increase in BDNF expression in the CA1-CA4 regions of the hippocampus and in the dentate gyrus. However, pilocarpine increased NGF mRNA only in those neurons of the dentate gyrus and CA1-CA4 regions that also expressed NGF mRNA in the controls.(ABSTRACT TRUNCATED AT 250 WORDS)