Mechanism of TrkB-mediated hippocampal long-term potentiation

被引：378

作者：

Minichiello, L

Calella, AM

Medina, DL

Bonhoeffer, T

Klein, R

Korte, M

机构：

[1] European Mol Biol Lab, I-00016 Monterotondo, Italy

[2] Max Planck Inst Neurobiol, D-82152 Martinsried, Germany

来源：

NEURON | 2002年 / 36卷 / 01期

关键词：

D O I：

10.1016/S0896-6273(02)00942-X

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The TrkB receptor tyrosine kinase and its ligand, BDNF, have an essential role in certain forms of synaptic plasticity. However, the downstream pathways required to mediate these functions are unknown. We have studied mice with a targeted mutation in either the Shc or the phospholipase Cgamma (PLCgamma) docking sites of TrkB (trkB(SHC/SHC) and trkB(PLC/PLC) mice). We found that hippocampal long-term potentiation was impaired in trkB(PLC/PLC) mice, but not trkB(SHC/SHC) mice. BDNF stimulation of primary neurons derived from trkB(PLC/PLC) mice fully retained their ability to activate MAP kinases, whereas induction of CREB and CaMKIV phosphorylation was strongly impaired. The opposite effect was observed in trkB(SHC/SHC) neurons, suggesting that MAPKs and CREB act in parallel pathways. Our results provide genetic evidence that TrkB mediates hippocampal plasticity via recruitment of PLCgamma, and by subsequent phosphorylation of CaMKIV and CREB.

引用

页码：121 / 137

页数：17

共 59 条

[1] Expression of constitutively active CREB protein facilitates the late phase of long-term potentiation by enhancing synaptic capture [J].