Brain-Derived Neurotrophic Factor Modulates Hippocampal Synaptic Transmission by Increasing N-methyl-D-Aspartic Acid Receptor Activity

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 95; no. 17; pp. 10235 - 10239
• Main Authors: Levine, Eric S., Crozier, Robert A., Black, Ira B., Plummer, Mark R.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 18.08.1998; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences
• Subjects: Acetylcholine - pharmacology; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid - pharmacology; Animals; Biological Sciences; Brain; Brain-Derived Neurotrophic Factor - pharmacology; Brain-Derived Neurotrophic Factor - physiology; Cell lines; Cells, Cultured; Dizocilpine Maleate - pharmacology; Glutamic Acid - pharmacology; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiology; Long term potentiation; N methyl D aspartate receptors; N-Methylaspartate - pharmacology; Nerve Growth Factors - pharmacology; Neurology; Neurons; Neuroscience; Neurotrophin 3; Phosphorylation; Pipettes; Rats; Receptors; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - drug effects; Receptors, N-Methyl-D-Aspartate - physiology; Synaptic transmission; Synaptic Transmission - drug effects; Synaptic Transmission - physiology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.17.10235

Neurotrophins (NTs) have recently been found to regulate synaptic transmission 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, currents 3-fold and increased N-methyl-D-aspartic acid (NMDA) receptor open probability. Activation of trkB NT receptors was critical, as glutamate currents were not affected by nerve growth factor or NT-3, and increased 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, further suggesting that NTs modulate synaptic efficacy via changes in NMDA receptor function.