Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Neuroscience Research Institute and Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
Curr Biol. 2023 Jun 19;33(12):2397-2406.e6. doi: 10.1016/j.cub.2023.04.055. Epub 2023 May 17.
Acute avoidance of dangerous temperatures is critical for animals to prevent or minimize injury. Therefore, surface receptors have evolved to endow neurons with the capacity to detect noxious heat so that animals can initiate escape behaviors. Animals including humans have evolved intrinsic pain-suppressing systems to attenuate nociception under some circumstances. Here, using Drosophila melanogaster, we uncovered a new mechanism through which thermal nociception is suppressed. We identified a single descending neuron in each brain hemisphere, which is the center for suppression of thermal nociception. These Epi neurons, for Epione-the goddess of soothing of pain-express a nociception-suppressing neuropeptide Allatostatin C (AstC), which is related to a mammalian anti-nociceptive peptide, somatostatin. Epi neurons are direct sensors for noxious heat, and when activated they release AstC, which diminishes nociception. We found that Epi neurons also express the heat-activated TRP channel, Painless (Pain), and thermal activation of Epi neurons and the subsequent suppression of thermal nociception depend on Pain. Thus, while TRP channels are well known to sense noxious temperatures to promote avoidance behavior, this work reveals the first role for a TRP channel for detecting noxious temperatures for the purpose of suppressing rather than enhancing nociception behavior in response to hot thermal stimuli.
急性避免危险温度对动物至关重要，可防止或最小化伤害。因此，表面受体已经进化，赋予神经元检测有害热的能力，以便动物可以启动逃避行为。包括人类在内的动物已经进化出内在的疼痛抑制系统，以便在某些情况下减轻伤害感受。在这里，我们使用黑腹果蝇揭示了一种新的热伤害感受抑制机制。我们在每个大脑半球中鉴定出单个下行神经元，这是热伤害感受抑制的中枢。这些 Epione 神经元（源自希腊语，意为“缓解疼痛的女神”）表达一种伤害感受抑制神经肽 Allatostatin C（AstC），它与哺乳动物的抗伤害感受肽 somatostatin 有关。Epi 神经元是有害热的直接传感器，当被激活时，它们会释放 AstC，从而减轻伤害感受。我们发现 Epi 神经元还表达热激活的 TRP 通道 Painless（Pain），Epi 神经元的热激活和随后的热伤害感受抑制依赖于 Pain。因此，虽然 TRP 通道众所周知可感知有害温度以促进逃避行为，但这项工作揭示了第一个用于检测有害温度的 TRP 通道的作用，目的是抑制而不是增强对热刺激的伤害感受行为。
