Gottschalk W, Pozzo-Miller L D, Figurov A, Lu B
Unit on Synapse Development and Plasticity, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
J Neurosci. 1998 Sep 1;18(17):6830-9. doi: 10.1523/JNEUROSCI.18-17-06830.1998.
In addition to the regulation of neuronal survival and differentiation, neurotrophins may play a role in synapse development and plasticity. Application of brain-derived neurotrophic factor (BDNF) promotes long-term potentiation (LTP) in CA1 synapses of neonatal hippocampus, which otherwise exhibit only short-term potentiation. This is attributable, at least in part, to an attenuation of the synaptic fatigue induced by high-frequency stimulation (HFS). However, the prevention of synaptic fatigue by BDNF could be mediated by an attenuation of synaptic vesicle depletion from presynaptic terminals and/or a reduction of the desensitization of postsynaptic receptors. Here we provide evidence supporting a presynaptic effect of BDNF. The effect of BDNF on synaptic fatigue depended on the stimulation frequency, not on the stimulus duration nor on the number of stimulation pulses. BDNF was only effective when the synapses were stimulated at frequencies >50 Hz. Treatment with BDNF also potentiated paired-pulse facilitation (PPF), a parameter reflecting changes in the properties of presynaptic terminals. This effect of BDNF was restricted only to PPF elicited with interpulse intervals </=20 msec. Changes in the extracellular calcium concentration altered the magnitude of the BDNF effect on PPF and synaptic responses to HFS, suggesting that BDNF regulates neurotransmitter release. When the desensitization of glutamate receptors was blocked by cyclothiazide or aniracetam, the BDNF potentiation of the synaptic responses to HFS was unaltered. Taken together, these results suggest that BDNF acts presynaptically. When two pathways in the same slice were monitored simultaneously, BDNF treatment potentiated the tetanized pathway without affecting the synaptic efficacy of the untetanized pathway. The selective potentiation of high-frequency transmission by BDNF appears to contribute directly to the effect of BDNF on LTP rather than indirectly by inducing the release of additional diffusible factors. The preferential potentiation of highly active synapses by BDNF may have implications in the Hebbian mechanism of synaptic plasticity.
除了调节神经元的存活和分化外，神经营养因子可能在突触发育和可塑性中发挥作用。应用脑源性神经营养因子（BDNF）可促进新生海马体CA1突触中的长时程增强（LTP），否则这些突触仅表现出短时程增强。这至少部分归因于高频刺激（HFS）诱导的突触疲劳的减轻。然而，BDNF对突触疲劳的预防可能是通过减轻突触前终末的突触小泡耗竭和/或减少突触后受体的脱敏来介导的。在此，我们提供了支持BDNF突触前效应的证据。BDNF对突触疲劳的影响取决于刺激频率，而不取决于刺激持续时间或刺激脉冲数。只有当突触以>50 Hz的频率刺激时，BDNF才有效。用BDNF处理还增强了双脉冲易化（PPF），这是一个反映突触前终末特性变化的参数。BDNF的这种作用仅限于脉冲间隔≤20毫秒时引发的PPF。细胞外钙浓度的变化改变了BDNF对PPF和对HFS的突触反应的影响程度，表明BDNF调节神经递质释放。当谷氨酸受体的脱敏被环噻嗪或茴拉西坦阻断时,BDNF对HFS突触反应的增强作用未改变。综上所述，这些结果表明BDNF在突触前起作用。当同时监测同一切片中的两条通路时，BDNF处理增强了强直刺激的通路，而不影响未强直刺激通路的突触效能。BDNF对高频传递的选择性增强似乎直接促成了BDNF对LTP的作用，而不是通过诱导额外的可扩散因子的释放间接促成。BDNF对高活性突触的优先增强作用可能对突触可塑性的赫布机制有影响。
