Brain-derived neurotrophic factor rapidly enhances synaptic transmission in hippocampal neurons via postsynaptic tyrosine kinase receptors.
Although neurotrophins are primarily associated with long-term effects on neuronal survival and differentiation, recent studies have shown that acute changes in synaptic transmission can also be produced. In the hippocampus, an area critically involved in learning and memory, we have found that brain-derived neurotrophic factor (BDNF) rapidly enhanced synaptic efficacy through a previously unreported mechanism--increased postsynaptic responsiveness via a phosphorylation-dependent pathway. Within minutes of BDNF application to cultured hippocampal neurons, spontaneous firing rate was dramatically increased, as were the frequency and amplitude of excitatory postsynaptic currents. The increased frequency of postsynaptic currents resulted from the change in presynaptic firing. However, the increased amplitude was postsynaptic in origin because it was selectively blocked by intracellular injection of the tyrosine kinase receptor (Ntrk2/TrkB) inhibitor K-252a and potentiated by injection of the phosphatase inhibitor okadaic acid. These results suggest a role for BDNF in the modulation of synaptic transmission in the hippocampus.
Levine
E S
ES
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School/University of Medicine and Dentistry of New Jersey, Piscataway 08854, USA.
Dreyfus
C F
CF
Black
I B
IB
Plummer
M R
MR
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles / Q000494:pharmacology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004988:Ethers, Cyclic / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000502:physiology*; D026121:Indole Alkaloids; D007700:Kinetics; D009414:Nerve Growth Factors / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019319:Okadaic Acid; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D002227:Carbazoles; D004988:Ethers, Cyclic; D026121:Indole Alkaloids; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D019319:Okadaic Acid; C049985:staurosporine aglycone; D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C; D017027:Protein Tyrosine Phosphatases