Postsynaptic TRPC1 Function Contributes to BDNF-Induced Synaptic Potentiation at the Developing Neuromuscular Junction

作者：McGurk Julie S; Shim Sangwoo; Kim Ju Young; Wen Zhexing; Song Hongjun; Ming Guo li^*

来源：Journal of Neuroscience, 2011, 31(41): 14754-14762.

DOI：10.1523/JNEUROSCI.3599-11.2011

Brain-derived neurotrophic factor (BDNF) induces synaptic potentiation at both neuromuscular junctions (NMJs) and synapses of the CNS through a Ca(2+)-dependent pathway. The molecular mechanism underlying BDNF-induced synaptic potentiation, especially the regulation of Ca(2+) 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 Ca(2+) elevation and full synaptic potentiation at the NMJ, suggesting a previously underappreciated postsynaptic function of Ca(2+) 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 Ca(2+) 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 Ca(2+) elevation required for BDNF-induced synaptic plasticity.

• 出版日期2011-10-12