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 (Na_Vs). 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.

光学刺激和抑制神经元的能力彻底改变了神经科学研究。在这里，我们提出了一种直接、有效、用户友好的化学方法，用于光学沉默神经元。我们通过使用先前未公开的硝基苄基衍生的光裂解基团进行化学保护，使石房蛤毒素（STX）（一种天然存在的麻痹剂）暂时惰性。将笼中毒素 STX-bpc 暴露于短暂 (5 ms) 光脉冲，会快速释放强效 STX 衍生物，并短暂、空间精确地阻断电压门控钠通道 (Na _V s)。我们证明了 STX-bpc 在参数化操纵哺乳动物神经元和脑切片动作电位方面的功效。此外，我们通过剖析斑马鱼幼虫的感觉诱发游泳，展示了该试剂对抑制神经活动的有效性。 STX-bpc 的光解笼是一种直接的非侵入性、可逆、时空精确的神经沉默方法，无需遗传访问，从而消除了比较研究的障碍。