Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers
Optogenetic Visualization of Presynaptic Tonic Inhibition of Cerebellar Parallel Fibers
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DOI：
10.1523/jneurosci.4366-15.2016
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发表时间：
2016-05-25
影响因子：
5.3
通讯作者：
Augustine, George J.
中科院分区：
文献类型：
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作者：
Berglund, Ken;Wen, Lei;Augustine, George J.
在表达光遗传学氯化物指示剂 Clomeleon 的转基因小鼠的小脑颗粒细胞中对强直抑制进行成像。由于强直抑制作用的阻断，GABA(A) 受体的阻断显着降低了颗粒细胞中的氯离子浓度。这表明强直抑制是这些细胞的静息氯化物浓度的重要贡献者。强直抑制不仅在颗粒细胞体中观察到，而且在其轴突、平行纤维（PF）中也观察到。这种突触前强直性抑制可以在室温和生理温度下以及体内的切片中观察到，并且具有许多与在颗粒细胞体中测量的强直性抑制相同的特性。 GABA 应用表明，PF 至少具有两种类型的 GABA(A) 受体：一种是高亲和力受体，可被环境 GABA 激活并引起氯离子流入，介导强直抑制；另一种对 GABA 具有低亲和力，可引起氯离子流出，从而兴奋 PF。突触前强直抑制调节 PF 中谷氨酸的释放，因为 GABA(A) 受体阻断增强了 PF-浦肯野细胞突触处自发 EPSC 的频率和诱发 EPSC 的幅度。我们得出的结论是，PF 的强直抑制可能在调节小脑突触回路的信息流中发挥重要作用。相位信号和强直信号之间的这种串扰可能是突触回路微调的通用机制。
Tonic inhibition was imaged in cerebellar granule cells of transgenic mice expressing the optogenetic chloride indicator, Clomeleon. Blockade of GABA(A) receptors substantially reduced chloride concentration in granule cells due to block of tonic inhibition. This indicates that tonic inhibition is a significant contributor to the resting chloride concentration of these cells. Tonic inhibition was observed not only in granule cell bodies, but also in their axons, the parallel fibers (PFs). This presynaptic tonic inhibition could be observed in slices both at room and physiological temperatures, as well as in vivo, and has many of the same properties as tonic inhibition measured in granule cell bodies. GABA application revealed that PFs possess at least two types of GABA(A) receptor: one high-affinity receptor that is activated by ambient GABA and causes a chloride influx that mediates tonic inhibition, and a second with a low affinity for GABA that causes a chloride efflux that excites PFs. Presynaptic tonic inhibition regulates glutamate release from PFs because GABA(A) receptor blockade enhanced both the frequency of spontaneous EPSCs and the amplitude of evoked EPSCs at the PF-Purkinje cell synapse. We conclude that tonic inhibition of PFs could play an important role in regulating information flow though cerebellar synaptic circuits. Such cross talk between phasic and tonic signaling could be a general mechanism for fine tuning of synaptic circuits.