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Xiang Wu, Yuyan Jiang, Nicholas J Rommelfanger, Fan Yang, Qi Zhou, Rongkang Yin, Junlang Liu, Sa Cai, Wei Ren, Andrew Shin, Kyrstyn S Ong, Kanyi Pu, Guosong Hong
Department of Materials Science and Engineering, Stanford University, Stanford, CA, USA.
Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
Nat Biomed Eng. 2022 Jun;6(6):754-770. doi: 10.1038/s41551-022-00862-w. Epub 2022 Mar 21.
Neural circuitry is typically modulated via invasive brain implants and tethered optical fibres in restrained animals. Here we show that wide-field illumination in the second near-infrared spectral window (NIR-II) enables implant-and-tether-free deep-brain stimulation in freely behaving mice with stereotactically injected macromolecular photothermal transducers activating neurons ectopically expressing the temperature-sensitive transient receptor potential cation channel subfamily V member 1 (TRPV1). The macromolecular transducers, ~40 nm in size and consisting of a semiconducting polymer core and an amphiphilic polymer shell, have a photothermal conversion efficiency of 71% at 1,064 nm, the wavelength at which light attenuation by brain tissue is minimized (within the 400-1,800 nm spectral window). TRPV1-expressing neurons in the hippocampus, motor cortex and ventral tegmental area of mice can be activated with minimal thermal damage on wide-field NIR-II illumination from a light source placed at distances higher than 50 cm above the animal's head and at an incident power density of 10 mW mm. Deep-brain stimulation via wide-field NIR-II illumination may open up opportunities for social behavioural studies in small animals.
神经回路通常通过侵入性脑植入物和束缚动物的 tethered 光纤进行调制。在这里，我们展示了在第二个近红外光谱窗口 (NIR-II) 中的宽场照明，可以在通过立体注射大分子光热转导剂激活异位表达温度敏感瞬时受体电位阳离子通道亚家族 V 成员 1 (TRPV1) 的神经元的自由行为小鼠中实现植入和无绳深部脑刺激。大分子转导剂的尺寸约为 40nm，由半导体聚合物核和两亲聚合物壳组成，在 1064nm 的波长下具有 71%的光热转换效率，该波长下脑组织的光衰减最小（在 400-1800nm 光谱窗口内）。可以通过放置在距动物头部上方 50cm 以上的光源进行宽场 NIR-II 照明，以最小的热损伤激活小鼠海马、运动皮层和腹侧被盖区中表达 TRPV1 的神经元，并且入射功率密度为 10mW/mm。通过宽场 NIR-II 照明进行深部脑刺激可能为小动物的社会行为研究开辟机会。
