Archaerhodopsin Selectively and Reversibly Silences Synaptic Transmission through Altered pH.
Archaerhodopsin Selectively and Reversibly Silences Synaptic Transmission through Altered pH.
复制标题
DOI：
10.1016/j.celrep.2016.07.057
复制
发表时间：
2016-08-23
期刊：
影响因子：
8.8
通讯作者：
Shipton OA
中科院分区：
文献类型：
--
作者：
El-Gaby M;Zhang Y;Wolf K;Schwiening CJ;Paulsen O;Shipton OA
允许急性和选择性沉默体内突触传递的工具对于理解特定行为的突触基础将是非常宝贵的。在这里，我们表明，突触前表达的质子泵古视紫红质，使强大的，选择性的，可逆的光遗传学突触沉默与快速启动和抵消。双光子荧光成像显示，这种效果是伴随着一个短暂的pH值的增加，仅限于古紫质表达终扣。至关重要的是，钳制细胞内pH值废除突触沉默，而不影响古紫质介导的超极化电流，表明pH值的变化介导的突触沉默效应。为了验证这种技术的实用性，我们使用了试验有限的，古视紫红质介导的沉默，揭示了CA 3-CA 1突触的传入来源于左CA 3的要求，但不是那些从右CA 3，在长期记忆任务的性能。这些结果突出了突触传递的光遗传学、pH介导的沉默作为解剖行为动物中突触功能的时空选择性方法。古视紫红质选择性和可逆地沉默突触传递古视紫红质沉默突触传递而不阻断动作电位古视紫红质通过pH值的变化介导突触沉默突触沉默揭示了学习过程中CA 3-CA 1突触之间的差异El-Gaby et al.证明古视紫红质可以通过pH的变化而不是超极化来急性地和选择性地沉默突触传递。这个工具在行为动物中的应用揭示了从左侧CA 3到CA 1神经元的突触在长期记忆表现中的必要性，而不是从右侧CA 3。
Tools that allow acute and selective silencing of synaptic transmission in vivo would be invaluable for understanding the synaptic basis of specific behaviors. Here, we show that presynaptic expression of the proton pump archaerhodopsin enables robust, selective, and reversible optogenetic synaptic silencing with rapid onset and offset. Two-photon fluorescence imaging revealed that this effect is accompanied by a transient increase in pH restricted to archaerhodopsin-expressing boutons. Crucially, clamping intracellular pH abolished synaptic silencing without affecting the archaerhodopsin-mediated hyperpolarizing current, indicating that changes in pH mediate the synaptic silencing effect. To verify the utility of this technique, we used trial-limited, archaerhodopsin-mediated silencing to uncover a requirement for CA3-CA1 synapses whose afferents originate from the left CA3, but not those from the right CA3, for performance on a long-term memory task. These results highlight optogenetic, pH-mediated silencing of synaptic transmission as a spatiotemporally selective approach to dissecting synaptic function in behaving animals. Archaerhodopsin selectively and reversibly silences synaptic transmission Archaerhodopsin silences synaptic transmission without blocking action potentials Archaerhodopsin mediates synaptic silencing through changes in pH Synaptic silencing reveals distinctions among CA3-CA1 synapses during learning El-Gaby et al. demonstrate that archaerhodopsin can acutely and selectively silence synaptic transmission through changes in pH rather than hyperpolarization. Application of this tool in behaving animals reveals a necessity for synapses from the left CA3 onto CA1 neurons, but not from the right CA3, in long-term memory performance.