Jin Shuang, Li Jiazhi, Jiang Luyue, Ye Yifei, Ma Chenguang, Yang Yingkang, Su Haoyang, Gao Lusha, Ni Min, Zhao Yiping, Tian Ye, Li Gen, Shi Jinwei, Zhang Kaihuan, Tang Pengyi, Yuan Yu, Lai Bin, Chen Ming, Sun Liuyang
2020 X-Lab, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, Shanghai 200050, China.
School of Integrated Circuits, University of Chinese Academy of Sciences, Beijing 100049, China.
Sci Adv. 2025 Jun 13;11(24):eadt4771. doi: 10.1126/sciadv.adt4771.
Noninvasive transcranial neuromodulation of deep brain regions is a longstanding goal in neuroscience. While optogenetics enables remote neural control, it is constrained by shallow tissue penetration of visible light and delayed onset due to required opsin expression. Here, we introduce a neuromodulation technique using hybrid upconversion and photovoltaic (HUP) nanoparticles, which eliminates the need for genetic modification and affords near-infrared (NIR) activation of neurons in wild-type mice. This method converts deeply penetrating NIR light into localized electrical stimuli, enabling immediate and precise modulation in deep brain. In vitro patch-clamp experiments confirm neuronal activation upon HUP application. In vivo, we achieve remote NIR neuromodulation in the medial septum and ventral tegmental area 7 days postinjection, effectively modulating neuronal activity, suppressing seizures, and triggering dopamine release. This minimally invasive approach offers a versatile tool kit for investigating neural processes in mammals, with potential applications across diverse brain regions through customizable nanoparticle engineering.
对深部脑区进行非侵入性经颅神经调节是神经科学领域长期以来的目标。虽然光遗传学能够实现远程神经控制，但它受到可见光在组织中穿透深度较浅以及由于需要视蛋白表达而导致起效延迟的限制。在此，我们介绍一种使用上转换与光伏混合（HUP）纳米颗粒的神经调节技术，该技术无需基因改造，可在野生型小鼠中实现对神经元的近红外（NIR）激活。这种方法将穿透性强的近红外光转化为局部电刺激，能够在深部脑区实现即时且精确的调节。体外膜片钳实验证实了应用HUP后神经元的激活。在体内，注射后7天我们在内侧隔区和腹侧被盖区实现了远程近红外神经调节，有效调节了神经元活动、抑制了癫痫发作并触发了多巴胺释放。这种微创方法为研究哺乳动物的神经过程提供了一个多功能工具包，通过可定制的纳米颗粒工程，在不同脑区具有潜在应用。
