Behavioral control through the direct, focal silencing of neuronal activity

IF 6.6 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
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引用次数: 0

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.

Abstract Image

Abstract Image

通过直接抑制神经元活动控制行为
光学刺激和抑制神经元的能力给神经科学研究带来了革命性的变化。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。我们用一种以前未公开的硝基苄基光可裂解基团进行化学保护,使天然麻痹剂沙西毒素(STX)暂时失去活性。将笼状毒素 STX-bpc 暴露于短暂(5 毫秒)的光脉冲下,会迅速释放出一种强效 STX 衍生物,并对电压门控钠通道(NaVs)产生瞬时、空间精确的阻断作用。我们展示了 STX-bpc 在哺乳动物神经元和脑片中参数化操纵动作电位的功效。此外,我们还通过解剖幼年斑马鱼的感觉诱发游泳,展示了这种试剂在沉默神经活动方面的有效性。STX-bpc 的光诱导是一种非侵入性、可逆、时空精确神经沉默的直接方法,无需基因接入,从而消除了比较研究的障碍。
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来源期刊
Cell Chemical Biology
Cell Chemical Biology Biochemistry, Genetics and Molecular Biology-Molecular Medicine
CiteScore
14.70
自引率
2.30%
发文量
143
期刊介绍: Cell Chemical Biology, a Cell Press journal established in 1994 as Chemistry & Biology, focuses on publishing crucial advances in chemical biology research with broad appeal to our diverse community, spanning basic scientists to clinicians. Pioneering investigations at the chemistry-biology interface, the journal fosters collaboration between these disciplines. We encourage submissions providing significant conceptual advancements of broad interest across chemical, biological, clinical, and related fields. Particularly sought are articles utilizing chemical tools to perturb, visualize, and measure biological systems, offering unique insights into molecular mechanisms, disease biology, and therapeutics.
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