Brain-derived neurotrophic factor increases activity of NR2B-containing N-methyl-D-aspartate receptors in excised patches from hippocampal neurons.
Growth factors, including members of the neurotrophin gene family, play a central role in the regulation of neuronal survival and differentiation during development. In addition to these relatively long-term actions of neurotrophins, recent studies have shown that these factors also rapidly modulate synaptic transmission. Brain-derived neurotrophic factor (BDNF), in particular, regulates both pre- and postsynaptic aspects of hippocampal synaptic transmission. The postsynaptic effects include an increase in glutamate responsiveness, mediated by the N-methyl-D-aspartate (NMDA) glutamate receptor subtype. It is not clear, however, where BDNF-trkB signal transduction is initiated, because trkB receptors are located in both pre- and postsynaptic membranes. In the present study, we used excised membrane patches from cultured hippocampal neurons to determine whether BDNF directly modulates postsynaptic NMDA receptor activity. The results indicate that acute exposure to BDNF increases NMDA single channel open probability via postsynaptic trkB receptors and that this effect is dependent on the presence of the NR2B subunit of the NMDA receptor.
Levine
E S
ES
Department of Pharmacology and Program in Neuroscience, University of Connecticut Health Center, Farmington 06030-6125, USA. eslevine@neuron.uchc.edu
Kolb
J E
JE
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; C010739:ifenprodil