Early presynaptic and late postsynaptic components contribute independently to brain-derived neurotrophic factor-induced synaptic plasticity.
Trophin-induced synaptic plasticity consists of both presynaptic and postsynaptic processes. The potential interdependence of these mechanisms and their temporal relationships are undefined. The synaptic vesicle protein Rab3A is required for the early, initial 10 min phase but not for the later phase of BDNF-enhanced transmission. We now examine the temporal distinction and mechanistic relationships between these phases of BDNF action. Rab3A mutant cells did not exhibit increased miniature EPSC frequency in response to BDNF in cell culture, indicating an absence of the presynaptic component. In contrast, BDNF enhanced postsynaptic glutamate-induced current in the mutant neurons as in the wild type, indicating that the postsynaptic component of the response was intact. Finally, the postsynaptic NMDA receptor subunit NR2B was phosphorylated at Tyr1472 by BDNF in Rab3A knock-outs, as shown previously in wild type. Our results are the first to demonstrate that presynaptic and postsynaptic components of BDNF-enhanced synaptic activity are independent and temporally distinct.
Alder
Janet
J
Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey 08854-5635, USA.
Thakker-Varia
Smita
S
Crozier
Robert A
RA
Shaheen
Aisha
A
Plummer
Mark R
MR
Black
Ira B
IB
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000166:cytology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011247:Pregnancy; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism; D013997:Time Factors; D020826:rab3A GTP-Binding Protein / Q000172:deficiency
D019208:Brain-Derived Neurotrophic Factor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D020826:rab3A GTP-Binding Protein