Data from: Optogenetic recruitment of dorsal raphe serotonergic neurons acutely decreases mechanosensory responsivity in behaving mice

The inhibition of sensory responsivity is considered a core serotonin function, yet this hypothesis lacks direct support due to methodological obstacles. We adapted an optogenetic approach to induce acute, robust and specific firing of dorsal raphe serotonergic neurons. In vitro, the responsiveness of individual dorsal raphe serotonergic neurons to trains of light pulses varied with frequency and intensity as well as between cells, and the photostimulation protocol was therefore adjusted to maximize their overall output rate. In vivo, the photoactivation of dorsal raphe serotonergic neurons gave rise to a prominent light-evoked field response that displayed some sensitivity to a 5-HT1A agonist, consistent with autoreceptor inhibition of raphe neurons. In behaving mice, the photostimulation of dorsal raphe serotonergic neurons produced a rapid and reversible decrease in the animals’ responses to plantar stimulation, providing a new level of evidence that serotonin gates sensory-driven responses.

感觉反应性抑制被视作血清素的核心功能之一，但该假说因方法学障碍尚未获得直接实验证据支撑。我们优化了光遗传学（optogenetic）技术方案，以诱导中缝背核血清素能神经元产生急性、强效且特异性的动作电位放电。体外实验中，单个中缝背核血清素能神经元对光脉冲串的响应特性随刺激频率、强度及细胞个体差异而变化，因此我们调整了光刺激方案以最大化神经元的整体放电效率。体内实验中，激活中缝背核血清素能神经元可引发显著的光诱导电场电位反应，该反应对5-羟色胺1A（5-HT1A）受体激动剂具有一定敏感性，这与中缝核神经元的自身受体抑制效应相符。在行为学实验小鼠中，光激活中缝背核血清素能神经元可快速且可逆地降低动物对足底刺激的响应，这为血清素门控感觉驱动反应的假说提供了新的直接实验依据。