Berninger B, Schinder A F, Poo M M
Department of Biology, University of California San Diego, La Jolla 92093-0357, USA.
Learn Mem. 1999 May-Jun;6(3):232-42.
Recent studies have implicated brain-derived neurotrophic factor (BDNF) in use-dependent modification of hippocampal synapses. BDNF can rapidly potentiate synaptic transmission at glutamatergic synapses by enhancing transmitter release. Using simultaneous perforated patch recording from pairs and triplets of glutamatergic hippocampal neurons, we have examined how the initial state of the glutamatergic synapse determines its susceptibility to synaptic modification by BDNF. We found that the degree of synaptic potentiation by BDNF depends on the initial reliability and strength of the synapse: Relatively weak connections were strongly potentiated, whereas the effect was markedly reduced at stronger synapses. The degree of BDNF-induced potentiation strongly correlated with the initial coefficient of variation (CV) of the amplitude of excitatory postsynaptic currents (EPSCs) and inversely correlated with the initial paired-pulse facilitation, suggesting that synapses with lower release probability (Pr) are more susceptible to the action of BDNF. To determine whether saturation of Pr could have masked the potentiation effect of BDNF in the stronger synapses, we lowered the initial Pr either by reducing the extracellular Ca2+ concentration ([Ca2+]o) or by bath application of adenosine. Synapses that were initially strong remained unaffected by BDNF under these conditions of reduced Pr. Thus, the lack of BDNF effect on synaptic efficacy cannot simply be accounted for by saturation of Pr, but rather may be due to intrinsic changes associated with synaptic maturation that might covary with Pr. Finally, the dependence on initial synaptic strength was also found for divergent outputs of the same presynaptic neuron, suggesting that synaptic terminals with different degrees of responsiveness to BDNF can coexist within in the same neuron.
最近的研究表明，脑源性神经营养因子（BDNF）参与海马突触的使用依赖性修饰。BDNF可通过增强递质释放，迅速增强谷氨酸能突触处的突触传递。利用对谷氨酸能海马神经元对和三联体进行同步穿孔膜片钳记录，我们研究了谷氨酸能突触的初始状态如何决定其对BDNF介导的突触修饰的敏感性。我们发现，BDNF介导的突触增强程度取决于突触的初始可靠性和强度：相对较弱的连接被强烈增强，而在较强的突触处这种效应明显减弱。BDNF诱导的增强程度与兴奋性突触后电流（EPSCs）幅度的初始变异系数（CV）密切相关，与初始双脉冲易化呈负相关，这表明释放概率（Pr）较低的突触对BDNF的作用更敏感。为了确定Pr的饱和是否掩盖了BDNF在较强突触中的增强作用，我们通过降低细胞外Ca2+浓度（[Ca2+]o）或通过浴灌腺苷来降低初始Pr。在这些Pr降低的条件下，最初较强的突触不受BDNF影响。因此，BDNF对突触效能缺乏影响不能简单地用Pr的饱和来解释，而可能是由于与突触成熟相关的内在变化，这些变化可能与Pr共同变化。最后，在同一突触前神经元的发散性输出中也发现了对初始突触强度的依赖性，这表明对BDNF反应程度不同的突触终末可以共存于同一神经元内。
