Kang H, Welcher A A, Shelton D, Schuman E M
Howard Hughes Medical Institute, Division of Biology, California Institute of Technology, Pasadena 91125, USA.
Neuron. 1997 Sep;19(3):653-64. doi: 10.1016/s0896-6273(00)80378-5.
We examined the role of TrkB ligands in hippocampal long-term potentiation (LTP) using function-blocking TrkB antiserum (Ab) and Trk-IgG fusion proteins. Incubation of hippocampal slices with TrkB Ab had no effect on basal synaptic transmission, short-term plasticity, or LTP induced by several trains of tetanic stimulation. The TrkB Ab-treated slices, however, showed significant deficits in LTP induced by either theta-burst stimulation (TBS) or "pairing." Slices exposed to the same number of inducing stimuli, delivered either as TBS or as a single 100 Hz epoch, only exhibited TrkB-sensitive LTP when TBS was used, indicating that the temporal pattern of stimulation determines the neurotrophin dependence. The late phase of LTP (2-3 hr) was also significantly impaired in slices pretreated with TrkB Ab or a TrkB-IgG. The application of a TrkB-IgG 30 min after LTP induction caused previously potentiated synaptic transmission to return to baseline levels, indicating that TrkB ligands are required to maintain LTP for up to 1 hr after induction. Taken together, these results indicate that both the temporal patterns of synaptic activity and the different temporal phases of synaptic enhancement are important in determining the neurotrophin dependence of plasticity in the hippocampus.
我们使用功能阻断性TrkB抗血清（Ab）和Trk-IgG融合蛋白研究了TrkB配体在海马体长期增强（LTP）中的作用。用TrkB Ab孵育海马体切片对基础突触传递、短期可塑性或由多串强直刺激诱导的LTP没有影响。然而，经TrkB Ab处理的切片在由theta爆发刺激（TBS）或“配对”诱导的LTP中表现出显著缺陷。暴露于相同数量诱导刺激的切片，无论是作为TBS还是作为单个100 Hz时段给予，只有在使用TBS时才表现出TrkB敏感的LTP，这表明刺激的时间模式决定了神经营养因子的依赖性。在用TrkB Ab或TrkB-IgG预处理的切片中，LTP的后期阶段（2-3小时）也受到显著损害。在LTP诱导后30分钟应用TrkB-IgG导致先前增强的突触传递恢复到基线水平，表明TrkB配体是在诱导后长达1小时维持LTP所必需的。综上所述，这些结果表明突触活动的时间模式和突触增强的不同时间阶段在决定海马体可塑性的神经营养因子依赖性方面都很重要。
