Brain Science Institute RIKEN, Wako 351-0198 Japan.
J Neurosci. 2012 Sep 19;32(38):13189-99. doi: 10.1523/JNEUROSCI.1386-12.2012.
Properties and plasticity of inhibitory synapses on fast-spiking (FS) GABAergic (FS-GABA) interneurons in layer II/III of the mouse visual cortex were examined in cortical slices by whole-cell recordings of IPSCs or IPSPs evoked by activation of presynaptic FS or non-FS GABAergic interneurons. Unitary IPSCs (uIPSCs) evoked by action potentials of FS-GABA neurons have shorter onset latency, faster rising slope, higher peak amplitude, and faster decay time than those evoked by action potentials of non-FS-GABA neurons. Tetanic activation of presynaptic FS-GABA neurons induced long-term potentiation (LTP) of uIPSCs, whereas that of presynaptic non-FS-GABA neurons did not induce LTP, indicating that long-term plasticity of inhibitory synapses on FS-GABA neurons is pathway specific. For further analysis of inhibitory synaptic plasticity, IPSPs evoked by electrical stimulation of an adjacent site in the cortex were recorded from FS-GABA neurons. Theta burst stimulation induced LTP of IPSPs in 12 of 14 FS-GABA neurons. The paired-pulse stimulation protocol and coefficient of variation analysis indicated that this form of LTP may be presynaptic in origin. Filling postsynaptic cells with a Ca(2+) chelator did not block the induction of LTP, suggesting no involvement of postsynaptic Ca(2+) rise. Also, this form of LTP was dependent neither on metabotropic glutamate receptors nor voltage-gated Ca(2+) channels of the L and T types. Further pharmacological analysis indicated that voltage-gated Ca(2+) channels other than the P/Q type, such as N and R types, were not involved in LTP, suggesting that P/Q-type channels are a candidate for factors inducing LTP of inhibitory synapses between FS-GABA neurons.
在小鼠视觉皮层 II/III 层的脑片上,通过全细胞膜片钳记录兴奋性中间神经元(FS-GABA)的 IPSC 或 IPSP,研究了这些中间神经元上抑制性突触的特性和可塑性。由 FS-GABA 神经元动作电位引发的单位 IPSC(uIPSCs)的起始潜伏期更短、上升斜率更快、峰值幅度更高、衰减时间更快,而由非 FS-GABA 神经元动作电位引发的 uIPSCs 则相反。对 FS-GABA 神经元的突触前进行强直刺激会诱导 uIPSCs 的长时程增强(LTP),而对非 FS-GABA 神经元的突触前进行强直刺激则不会诱导 LTP,这表明 FS-GABA 神经元上抑制性突触的长时程可塑性具有特定的通路特异性。为了进一步分析抑制性突触可塑性,我们从 FS-GABA 神经元上记录了由皮层相邻部位电刺激引发的 IPSP。θ爆发刺激可诱导 14 个 FS-GABA 神经元中的 12 个产生 IPSP 的 LTP。成对脉冲刺激方案和变异系数分析表明,这种形式的 LTP 可能起源于突触前。用 Ca(2+)螯合剂填充突触后细胞并不能阻断 LTP 的诱导,这表明没有涉及突触后 Ca(2+)的升高。此外,这种形式的 LTP 既不依赖于代谢型谷氨酸受体,也不依赖于 L 和 T 型电压门控 Ca(2+)通道。进一步的药理学分析表明,除了 P/Q 型之外的电压门控 Ca(2+)通道,如 N 和 R 型,都不参与 LTP,这表明 P/Q 型通道可能是诱导 FS-GABA 神经元之间抑制性突触 LTP 的因素之一。