title: Postsynaptic TRPC1 function contributes to BDNF-induced synaptic potentiation at the developing neuromuscular junction.
abstract: Brain-derived neurotrophic factor (BDNF) induces synaptic potentiation at both neuromuscular junctions (NMJs) and synapses of the CNS through a Ca2+ -dependent pathway. The molecular mechanism underlying BDNF-induced synaptic potentiation, especially the regulation of Ca2+ dynamics, is not well understood. Using the Xenopus NMJ in culture as a model system, we show that pharmacological inhibition or morpholino-mediated knockdown of Xenopus TRPC1 (XTRPC1) significantly attenuated the BDNF-induced potentiation of the frequency of spontaneous synaptic responses at the NMJ. Functionally, XTRPC1 was required specifically in postsynaptic myocytes for BDNF-induced Ca2+ elevation and full synaptic potentiation at the NMJ, suggesting a previously underappreciated postsynaptic function of Ca2+ signaling in neurotrophin-induced synaptic plasticity, in addition to its well established role at presynaptic sites. Mechanistically, blockade of the p75 neurotrophin receptor abolished BDNF-induced postsynaptic Ca2+ elevation and restricted BDNF-induced synaptic potentiation, while knockdown of the TrkB receptor in postsynaptic myocytes had no effect. Our study suggests that BDNF-induced synaptic potentiation involves coordinated presynaptic and postsynaptic responses and identifies TRPC1 as a molecular mediator for postsynaptic Ca2+ elevation required for BDNF-induced synaptic plasticity.
authors: The Solomon H. Snyder Department of Neuroscience, Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: Julie S
authors: JS
authors: McGurk
authors: Sangwoo
authors: S
authors: Shim
authors: Ju Young
authors: JY
authors: Kim
authors: Zhexing
authors: Z
authors: Wen
authors: Hongjun
authors: H
authors: Song
authors: Guo-Li
authors: GL
authors: Ming
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D018920:Coculture Techniques; D004558:Electric Stimulation / Q000379:methods; D004625:Embryo, Nonmammalian; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D018613:Microscopy, Confocal; D060172:Morpholinos / Q000494:pharmacology; D032342:Muscle Cells / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D020813:Receptor, trkB / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000235:genetics; D050052:TRPC Cation Channels / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D002121:Calcium Channel Blockers; D007093:Imidazoles; D060172:Morpholinos; D017475:Receptors, Nerve Growth Factor; D050052:TRPC Cation Channels; C502469:TRPC1 protein, Xenopus; D029867:Xenopus Proteins; D020813:Receptor, trkB; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium