Sahún Ignasi, Delgado-García José María, Amador-Arjona Alejandro, Giralt Albert, Alberch Jordi, Dierssen Mara, Gruart Agnès
Genes and Disease Program, Genomic Regulation Center, Universidad Pompeu Fabra, Barcelona Biomedical Research Park, 08003 Barcelona, Spain.
J Neurosci. 2007 Feb 28;27(9):2253-60. doi: 10.1523/JNEUROSCI.4055-06.2007.
Neurotrophins and their cognate receptors might serve as feedback regulators for the efficacy of synaptic transmission. We analyzed mice overexpressing TrkC (TgNTRK3) for synaptic plasticity and the expression of glutamate receptor subunits. Animals were conditioned using a trace [conditioned stimulus (CS), tone; unconditioned stimulus (US), shock] paradigm. A single electrical pulse presented to the Schaffer collateral-commissural pathway during the CS-US interval evoked a monosynaptic field EPSP (fEPSP) at ipsilateral CA1 pyramidal cells. In wild types, fEPSP slopes increased across conditioning sessions and decreased during extinction, being linearly related to learning evolution. In contrast, fEPSPs in TgNTRK3 animals reached extremely high values, not accompanied with a proportionate increase in their learning curves. Long-term potentiation evoked in conscious TgNTRK3 was also significantly longer lasting than in wild-type mice. These functional alterations were accompanied by significant changes in NR1 and NR2B NMDA receptor subunits, with no modification of NR1(Ser 896) or NR1(Ser 897) phosphorylation. No changes of AMPA and kainate subunits were detected. Results indicate that the NT-3/TrkC cascade could regulate synaptic transmission and plasticity through modulation of glutamatergic transmission at the CA3-CA1 synapse.
神经营养因子及其同源受体可能作为突触传递效能的反馈调节因子。我们分析了过表达TrkC（TgNTRK3）的小鼠的突触可塑性和谷氨酸受体亚基的表达。使用痕迹条件反射范式（条件刺激（CS），音调；非条件刺激（US），电击）对动物进行训练。在CS-US间隔期间，向Schaffer侧支-连合通路施加单个电脉冲，可在同侧CA1锥体细胞诱发单突触场兴奋性突触后电位（fEPSP）。在野生型小鼠中，fEPSP斜率在训练过程中增加，在消退过程中降低，且与学习进程呈线性相关。相比之下，TgNTRK3动物中的fEPSP达到极高值，但其学习曲线并未相应增加。清醒的TgNTRK3小鼠中诱发的长时程增强也比野生型小鼠持续时间长得多。这些功能改变伴随着NR1和NR2B NMDA受体亚基的显著变化，而NR1（Ser 896）或NR1（Ser 897）的磷酸化没有改变。未检测到AMPA和海人藻酸受体亚基的变化。结果表明，NT-3/TrkC级联可能通过调节CA3-CA1突触处的谷氨酸能传递来调节突触传递和可塑性。
