GLUTAMATE RELEASE CORRELATES WITH BRAIN-DERIVED NEUROTROPHIC FACTOR AND TRKB MESSENGER-RNA EXPRESSION IN THE CA1 REGION OF RAT HIPPOCAMPUS

Synthesis of the neurotrophic factor brain-derived neurotrophic factor (BDNF) and its receptor TrkB in the hippocampus have been proposed to be influenced by endogenous glutamate. To test this hypothesis we hav e investigated if increases in BDNF and trkB mRNAs are associated with changes in the synaptic release of glutamate in the dorsal hippocampu s in the conscious rat by combining the technique of in vivo microdial ysis with in situ hybridization histochemistry. A 35% and 66% increase in extracellular levels of glutamate in the dorsal CA1 region was det ected following injection into the lateral entorhinal cortex of 2.4 an d 9.6 mu g of the non-NMDA glutamate receptor agonist quisqualate, res pectively. The increase in glutamate was attenuated by local administr ation of tetrodotoxin (TTX) indicating neuronal origin. Levels of BDNF and trkB mRNAs were increased in the hippocampus in a dose-dependent fashion following the stimulations. The extracellular levels of glutam ate in individual animals correlated to the levels of BDNF and trkB mR NAs in the dorsal CA1 region of the hippocampus. This study provides f or the first time evidence of an entorhinal cortex influenced concentr ation-dependent relationship between the release of endogenous glutama te in vivo and neuronal expression of mRNAs for BDNF and its receptor trkB in the hippocampus.