Abstract：
The ability to optically stimulate and inhibit neurons has revolutionized neuroscience research. Here, we present a direct, potent, user-friendly chemical approach for optically silencing neurons. We have rendered saxitoxin (STX), a naturally occurring paralytic agent, transiently inert through chemical protection with a previously undisclosed nitrobenzyl-derived photocleavable group. Exposing the caged toxin, STX-bpc, to a brief (5 ms) pulse of light effects rapid release of a potent STX derivative and transient, spatially precise blockade of voltage-gated sodium channels (NaVs). We demonstrate the efficacy of STX-bpc for parametrically manipulating action potentials in mammalian neurons and brain slice. Additionally, we show the effectiveness of this reagent for silencing neural activity by dissecting sensory-evoked swimming in larval zebrafish. Photo-uncaging of STX-bpc is a straightforward method for non-invasive, reversible, spatiotemporally precise neural silencing without the need for genetic access, thus removing barriers for comparative research.
摘要：
光学刺激和抑制神经元的能力彻底改变了神经科学研究。这里,我们提出了一个直接的，强力，用于光学沉默神经元的用户友好的化学方法。我们已经提供了毒素（STX），一种自然产生的麻痹剂，通过用先前未公开的硝基苄基衍生的光可裂解基团进行化学保护而暂时惰性。暴露笼中的毒素，STX-bpc,一个短暂的（5毫秒）光脉冲效应快速释放一个有效的STX衍生物和瞬态，电压门控钠通道（Navs）的空间精确阻断。我们证明了STX-bpc在参数化操纵哺乳动物神经元和大脑切片中动作电位的功效。此外,我们通过解剖幼体斑马鱼的感觉诱发游泳，证明了该试剂沉默神经活动的有效性。STX-bpc的光解串是一种简单的非侵入性方法，可逆,时空精确的神经沉默，而不需要遗传通路，从而消除了比较研究的障碍。
