POSITIVE FEEDBACK BETWEEN ACETYLCHOLINE AND THE NEUROTROPHINS NERVE GROWTH-FACTOR AND BRAIN-DERIVED NEUROTROPHIC FACTOR IN THE RAT HIPPOCAMPUS

In the rat hippocampus, nerve growth factor (NGF) and brain-derived ne urotrophic factor (BDNF) are synthesized by neurons in an activity-dep endent manner. Glutamate receptor activation increases whereas GABAerg ic stimulation decreases NGF and BDNF mRNA levels. Here we demonstrate that NGF and BDNF mRNA and NGF protein are up-regulated in the rat hi ppocampus by the activation of muscarinic receptors. Conversely, NGF a nd BDNF enhance the release of acetylcholine (ACh) from rat hippocampa l synaptosomes containing the nerve endings of the septal cholinergic neurons. NGF also rapidly increases the high-affinity choline transpor t into synaptosomes. The reciprocal regulation of ACh, NGF and BDNF in the hippocampus suggests a novel molecular framework by which the neu rotrophins might influence synaptic plasticity.