Various neuromodulation approaches have been employed to alter neuronal spiking activity and thus regulate brain functions and alleviate neurological disorders. Infrared neural stimulation (INS) could be a potential approach for neuromodulation because it requires no tissue contact and possesses a high spatial resolution. However, the risk of overheating and an unclear mechanism hamper its application. Here we show that midinfrared stimulation (MIRS) with a specific wavelength exerts nonthermal, long-distance, and reversible modulatory effects on ion channel activity, neuronal signaling, and sensorimotor behavior. Patch-clamp recording from mouse neocortical pyramidal cells revealed that MIRS readily provides gain control over spiking activities, inhibiting spiking responses to weak inputs but enhancing those to strong inputs. MIRS also shortens action potential (AP) waveforms by accelerating its repolarization, through an increase in voltage-gated K⁺ (but not Na⁺) currents. Molecular dynamics simulations further revealed that MIRS-induced resonance vibration of –C=O bonds at the K⁺ channel ion selectivity filter contributes to the K⁺ current increase. Importantly, these effects are readily reversible and independent of temperature increase. At the behavioral level in larval zebrafish, MIRS modulates startle responses by sharply increasing the slope of the sensorimotor input–output curve. Therefore, MIRS represents a promising neuromodulation approach suitable for clinical application.

各种神经调节方法已被用于改变神经元尖峰活动，从而调节大脑功能并缓解神经系统疾病。红外神经刺激 (INS) 可能是一种潜在的神经调节方法，因为它不需要组织接触并具有高空间分辨率。然而，过热的风险和不明确的机制阻碍了其应用。在这里，我们展示了具有特定波长的中红外刺激 (MIRS) 对离子通道活动、神经元信号传导和感觉运动行为施加非热、长距离和可逆的调节作用。来自小鼠新皮质锥体细胞的膜片钳记录显示 MIRS 很容易提供对尖峰活动的增益控制，抑制对弱输入的尖峰反应，但增强对强输入的尖峰反应。⁺（但不是 Na ⁺）电流。分子动力学模拟进一步表明，在 K ⁺通道离子选择性过滤器处 MIRS 诱导的 –C=O 键共振有助于 K ⁺电流的增加。重要的是，这些影响很容易逆转并且与温度升高无关。在幼虫斑马鱼的行为水平上，MIRS 通过急剧增加感觉运动输入-输出曲线的斜率来调节惊吓反应。因此，MIRS 代表了一种适合临床应用的有前途的神经调节方法。