Tether-free photothermal deep-brain stimulation in freely behaving mice via wide-field illumination in the near-infrared-II window

• Main Authors: Wu, Xiang, Jiang, Yuyan, Rommelfanger, Nicholas J., Yang, Fan, Zhou, Qi, Yin, Rongkang, Liu, Junlang, Cai, Sa, Ren, Wei, Shin, Andrew, Ong, Kyrstyn S., Pu, Kanyi, Hong, Guosong
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2022
• Subjects: Engineering::Bioengineering; Science::Chemistry::Biochemistry; Deep Brain Stimulation; Near Infrared
• Online Access: https://hdl.handle.net/10356/162493
• Institution: Nanyang Technological University

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-2. Deep-brain stimulation via wide-field NIR-II illumination may open up opportunities for social behavioural studies in small animals.