BDNF enhancement of postsynaptic NMDA receptors is blocked by ethanol.
The neurotrophin brain-derived neurotrophic factor (BDNF) modulates several distinct aspects of synaptic transmission. Physiological and biochemical evidence implicates the NMDA glutamate receptor as one of the targets for BDNF modulation. In the present studies, murine brain slices containing hippocampus and neocortex were used to study the effects of BDNF on excitatory neurotransmission. Acute exposure to BDNF rapidly and reversibly enhanced the magnitude of NMDA-mediated, but not AMPA receptor-mediated, synaptic currents, specifically enhancing the activity of NMDA receptors containing the NR2B subunit. This effect of BDNF was dependent on activation of trkB neurotrophin receptors because similar effects were not seen with the related neurotrophins NT-3 or NGF. Furthermore, activation of trkB receptors in the postsynaptic neuron was required, as BDNF-induced potentiation was blocked by postsynaptic injection of a trk tyrosine kinase inhibitor. Interestingly, the effect of BDNF was also completely blocked by pretreatment with ethanol, even at concentrations of ethanol that had minimal direct effects on NMDA-mediated responses. These results provide a potential mechanism for the proposed role for BDNF in activity-dependent synaptic plasticity and, potentially, learning and memory processes.
Kolb
John E
JE
Department of Pharmacology, University of Connecticut Health Center, Farmington, Connecticut 06030, USA.
Trettel
Joseph
J
Levine
Eric S
ES
D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D019579:Neocortex / Q000166:cytology / Q000187:drug effects; D018408:Patch-Clamp Techniques / Q000379:methods; D010636:Phenols / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D019208:Brain-Derived Neurotrophic Factor; D002492:Central Nervous System Depressants; D018690:Excitatory Amino Acid Agonists; D010636:Phenols; D010880:Piperidines; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; C109643:Ro 25-6981; D000431:Ethanol; C056723:FG 9041; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid