Henneberger C, Kirischuk S, Grantyn R
Sensory and Developmental Physiology Group, Institute of Neurophysiology, Johannes-Mueller-Center of Physiology, Charité-University Medicine Berlin, Tucholskystr. 2, D-10117 Berlin, Germany.
Neuroscience. 2005;135(3):749-63. doi: 10.1016/j.neuroscience.2005.06.044. Epub 2005 Sep 8.
Brain-derived neurotrophic factor is known to modulate the function of GABAergic synapses, but the site of brain-derived neurotrophic factor action is still a matter of controversy. This study was aimed at further dissecting the functional alterations produced by brain-derived neurotrophic factor treatment of GABAergic synaptic connections in cultures of the murine superior colliculus. The functional consequences of long-term brain-derived neurotrophic factor treatment were assessed by analysis of unitary evoked and delayed inhibitory postsynaptic currents in response to high frequency stimulation of single axons. It was found that brain-derived neurotrophic factor facilitated the asynchronous release, but had no effect on the probability of evoked release, the size of the readily releasable pool, and the paired-pulse behavior of evoked inhibitory postsynaptic currents. However, the amplitudes of evoked inhibitory postsynaptic currents, delayed inhibitory postsynaptic currents and miniature inhibitory postsynaptic currents were significantly reduced. Non-stationary fluctuation analysis revealed a decrease in the open channel number at the miniature/evoked inhibitory postsynaptic current peak, but no effect on the mean GABA(A) receptor single channel conductance. Quantitative immunocytochemistry uncovered a significant elevation of presynaptic levels of glutamic acid decarboxylase 65. Together, these findings indicate that brain-derived neurotrophic factor treatment induces pre- as well as postsynaptic changes. What effect predominates will depend on the presynaptic activity pattern: at low activation rates brain-derived neurotrophic factor-treated synapses display a pronounced postsynaptic depression, but at high frequencies this depression is fully compensated by an enhancement of asynchronous release.
脑源性神经营养因子已知可调节γ-氨基丁酸能突触的功能，但脑源性神经营养因子的作用位点仍存在争议。本研究旨在进一步剖析脑源性神经营养因子处理对小鼠上丘培养物中γ-氨基丁酸能突触连接所产生的功能改变。通过分析对单根轴突高频刺激的单突触诱发抑制性突触后电流和延迟抑制性突触后电流，评估长期脑源性神经营养因子处理的功能后果。结果发现，脑源性神经营养因子促进了异步释放，但对诱发释放概率、易释放池大小及诱发抑制性突触后电流的双脉冲行为没有影响。然而，诱发抑制性突触后电流、延迟抑制性突触后电流和微小抑制性突触后电流的幅度均显著降低。非平稳波动分析显示，在微小/诱发抑制性突触后电流峰值处开放通道数量减少，但对平均γ-氨基丁酸A受体单通道电导没有影响。定量免疫细胞化学显示，谷氨酸脱羧酶65的突触前水平显著升高。这些结果共同表明，脑源性神经营养因子处理可诱导突触前和突触后改变。哪种效应占主导取决于突触前活动模式：在低激活率下，脑源性神经营养因子处理的突触表现出明显的突触后抑制，但在高频时，这种抑制可通过异步释放的增强而完全得到补偿。
