Currently available inhibitory optogenetic tools provide short and transient silencing of neurons, but they cannot provide long-lasting inhibition because of the requirement for high light intensities. Here we present an optimized blue-light-sensitive synthetic potassium channel, BLINK2, which showed good expression in neurons in three species. The channel is activated by illumination with low doses of blue light, and in our experiments it remained active over (tens of) minutes in the dark after the illumination was stopped. This activation caused long periods of inhibition of neuronal firing in ex vivo recordings of mouse neurons and impaired motor neuron response in zebrafish in vivo. As a proof-of-concept application, we demonstrated that in a freely moving rat model of neuropathic pain, the activation of a small number of BLINK2 channels caused a long-lasting (>30 min) reduction in pain sensation.

当前可用的抑制性光遗传学工具提供了神经元的短暂和短暂沉默，但是由于需要高的光强度，它们不能提供持久的抑制作用。在这里，我们介绍了一种优化的对蓝光敏感的合成钾通道BLINK2，该通道在三种物种的神经元中均表现出良好的表达。该通道通过低剂量的蓝光照射而被激活，并且在我们的实验中，在停止照明后的黑暗中，该通道在黑暗中持续了数十分钟。这种激活导致小鼠神经元离体记录中神经元放电的长期抑制和体内斑马鱼体内运动神经元反应的减弱。作为概念验证应用，我们证明了在自由移动的神经性疼痛大鼠模型中，