Yue Lupeng, Bao Chongyu, Zhang Libo, Zhang Fengrui, Zhou Wenqian, Iannetti Gian Domenico, Hu Li
State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.
State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China; Department of Psychology, University of Chinese Academy of Sciences, Beijing, China; Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Neuron. 2025 Mar 5;113(5):769-784.e6. doi: 10.1016/j.neuron.2024.12.011. Epub 2025 Jan 13.
Gamma-band oscillations (GBOs) in the primary somatosensory cortex (S1) play key roles in nociceptive processing. Yet, one crucial question remains unaddressed: what neuronal mechanisms underlie nociceptive-evoked GBOs? Here, we addressed this question using a range of somatosensory stimuli (nociceptive and non-nociceptive), neural recording techniques (electroencephalography in humans and silicon probes and calcium imaging in rodents), and optogenetics (alone or simultaneously with electrophysiology in mice). We found that (1) GBOs encoded pain intensity independent of stimulus intensity in humans, (2) GBOs in S1 encoded pain intensity and were triggered by spiking of S1 interneurons, (3) parvalbumin (PV)-positive interneurons preferentially tracked pain intensity, and critically, (4) PV S1 interneurons causally modulated GBOs and pain-related behaviors for both thermal and mechanical pain. These findings provide causal evidence that nociceptive-evoked GBOs preferentially encoding pain intensity are generated by PV interneurons in S1, thereby laying a solid foundation for developing GBO-based targeted pain therapies.
初级体感皮层（S1）中的伽马波段振荡（GBOs）在伤害性处理中起关键作用。然而，一个关键问题仍未得到解答：伤害性刺激诱发的GBOs背后的神经元机制是什么？在这里，我们使用一系列体感刺激（伤害性和非伤害性）、神经记录技术（人类的脑电图以及啮齿动物的硅探针和钙成像）以及光遗传学（单独使用或与小鼠的电生理学同时使用）来解决这个问题。我们发现：（1）在人类中，GBOs编码疼痛强度，与刺激强度无关；（2）S1中的GBOs编码疼痛强度，并由S1中间神经元的放电触发；（3）小白蛋白（PV）阳性中间神经元优先追踪疼痛强度，至关重要的是，（4）PV S1中间神经元因果性地调节热痛和机械痛的GBOs及疼痛相关行为。这些发现提供了因果证据，表明伤害性刺激诱发的、优先编码疼痛强度的GBOs是由S1中的PV中间神经元产生的，从而为开发基于GBOs的靶向疼痛治疗奠定了坚实基础。
