Chloride-dependent mechanisms of multimodal sensory discrimination and nociceptive sensitization in Drosophila.
Chloride-dependent mechanisms of multimodal sensory discrimination and nociceptive sensitization in Drosophila.
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DOI：
10.7554/elife.76863
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发表时间：
2023-01-23
期刊：
影响因子：
7.7
通讯作者：
Cox, Daniel N.
中科院分区：
文献类型：
--
作者：
Himmel, Nathaniel J.;Sakurai, Akira;Patel, Atit A.;Bhattacharjee, Shatabdi;Letcher, Jamin M.;Benson, Maggie N.;Gray, Thomas R.;Cymbalyuk, Gennady S.;Cox, Daniel N.
关键词：
个体感觉神经元可以被调谐到许多刺激，每个刺激驱动独特的刺激相关行为，并且多模式伤害感受器神经元区分潜在有害和无害刺激的能力对于生物体的生存非常重要。此外，区分有害和无害刺激的能力的中断可导致神经性疼痛。果蝇幼虫III类神经元是外周有害的冷伤害感受器和无害的触觉机械感受器;高水平的激活驱动冷诱发收缩（CT）行为，而低水平的激活导致一系列与触摸相关的行为。然而，它是未知的分子因素CIII多模态的基础。在这里，我们表明，TMEM 16/anoctamins制服和白色步行者（wwk; CG 15270）是所需的冷诱发CT，但不是触摸相关的行为，表明保守的作用anoctamins在伤害性感受。我们还证明CIII神经元利用非典型去极化氯电流来编码冷，并且ncc 69（NKCC 1的苍蝇同源物）的过表达导致与神经性致敏一致的表型，包括行为致敏和神经元过度兴奋，使果蝇CIII神经元成为未来研究神经性疼痛基本机制的候选系统。
Individual sensory neurons can be tuned to many stimuli, each driving unique, stimulus-relevant behaviors, and the ability of multimodal nociceptor neurons to discriminate between potentially harmful and innocuous stimuli is broadly important for organismal survival. Moreover, disruptions in the capacity to differentiate between noxious and innocuous stimuli can result in neuropathic pain. Drosophila larval class III (CIII) neurons are peripheral noxious cold nociceptors and innocuous touch mechanosensors; high levels of activation drive cold-evoked contraction (CT) behavior, while low levels of activation result in a suite of touch-associated behaviors. However, it is unknown what molecular factors underlie CIII multimodality. Here, we show that the TMEM16/anoctamins subdued and white walker (wwk; CG15270) are required for cold-evoked CT, but not for touch-associated behavior, indicating a conserved role for anoctamins in nociception. We also evidence that CIII neurons make use of atypical depolarizing chloride currents to encode cold, and that overexpression of ncc69—a fly homologue of NKCC1—results in phenotypes consistent with neuropathic sensitization, including behavioral sensitization and neuronal hyperexcitability, making Drosophila CIII neurons a candidate system for future studies of the basic mechanisms underlying neuropathic pain.