Wardle Rinda A, Poo Mu-ming
Division of Neurobiology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720-3200, USA.
J Neurosci. 2003 Sep 24;23(25):8722-32. doi: 10.1523/JNEUROSCI.23-25-08722.2003.
Brain-derived neurotrophic factor (BDNF) potentiates excitatory synapses in a variety of systems by promoting presynaptic transmitter release. The existing evidence indicates that BDNF attenuates inhibitory transmission, but reports differ considerably in their characterization of the effect and proposed mechanisms. We examined the effects of exogenously applied BDNF on EPSCs and IPSCs recorded from functionally identified neurons in dissociated rat hippocampal cultures. When recording from glutamatergic neurons, we found that BDNF exerted differential effects at excitatory versus inhibitory synapses: increasing amplitude of EPSCs but slightly decreasing that of IPSCs. Furthermore, when recording from GABAergic neurons, we found that BDNF increased the IPSC amplitude. That these differential BDNF effects reflect distinct presynaptic and postsynaptic mechanisms was suggested by the BDNF-induced changes in miniature EPSCs and IPSCs. An increased mini-frequency was found at all synapses, indicating elevated presynaptic transmitter secretion; a change in the amplitude of mini-IPSCs was found at GABAergic cells, suggesting postsynaptic modulation of GABA responses. Selective postsynaptic mechanisms were further examined by comparing the effect of BDNF on GABA-induced currents recorded from glutamatergic versus GABAergic cells. For GABAergic but not glutamatergic postsynaptic cells, BDNF induced a shift in the reversal potential (EIPSC) toward more positive levels, hence reducing the inhibitory action of IPSCs. This BDNF-induced effect correlates with the existing level of furosemide-sensitive K+-Cl- transport activity in the postsynaptic cell. Thus, BDNF may decrease the efficacy of inhibitory transmission by acute postsynaptic downregulation of Cl- transport, in addition to its well known presynaptic effect.
脑源性神经营养因子（BDNF）通过促进突触前递质释放，增强多种系统中的兴奋性突触。现有证据表明BDNF可减弱抑制性传递，但关于该效应的特征及提出的机制，各报告差异很大。我们研究了外源性应用BDNF对从离体大鼠海马培养物中功能鉴定的神经元记录的兴奋性突触后电流（EPSC）和抑制性突触后电流（IPSC）的影响。在记录谷氨酸能神经元时，我们发现BDNF对兴奋性和抑制性突触产生不同的影响：增加EPSC的幅度，但略微降低IPSC的幅度。此外，在记录γ-氨基丁酸能（GABA能）神经元时，我们发现BDNF增加了IPSC的幅度。微小EPSC和IPSC中BDNF诱导的变化表明，这些不同的BDNF效应反映了不同的突触前和突触后机制。在所有突触处均发现微小频率增加，表明突触前递质分泌增加；在GABA能细胞中发现微小IPSC的幅度发生变化，提示GABA反应的突触后调制。通过比较BDNF对从谷氨酸能和GABA能细胞记录的GABA诱导电流的影响，进一步研究了选择性突触后机制。对于GABA能而非谷氨酸能突触后细胞，BDNF诱导反转电位（EIPSC）向更正的水平偏移，从而降低IPSC的抑制作用。这种BDNF诱导的效应与突触后细胞中呋塞米敏感的K⁺-Cl⁻转运活性的现有水平相关。因此，BDNF除了其众所周知的突触前作用外，还可能通过急性突触后下调Cl⁻转运来降低抑制性传递的效力。
