BRAIN-DERIVED NEUROTROPHIC FACTOR MODULATES HIPPOCAMPAL SYNAPTIC TRANSMISSION BY INCREASING N-METHYL-D-ASPARTIC ACID RECEPTOR ACTIVITY

Neurotrophins (NTs) have recently been found to regulate synaptic tran smission in the hippocampus. Whole-cell and single-channel recordings from cultured hippocampal neurons revealed a mechanism responsible for enhanced synaptic strength. Specifically, brain-derived neurotrophic factor augmented glutamate evoked, but not acetylcholine-evoked, curre nts 3-fold and increased N-methyl-D-aspartic acid (NMDA) receptor open probability. Activation of trkB NT receptors was critical, as glutama te currents were not affected by nerve growth factor or NT-3, and incr eased open probability was prevented by the tyrosine kinase inhibitor K-252a. In addition, the NMDA receptor antagonist MK-801 blocked brain -derived neurotrophic factor enhancement of synaptic transmission, fur ther suggesting that NTs modulate synaptic efficacy via changes in NMD A receptor function.