Towards minimally invasive deep brain stimulation and imaging: A near-infrared upconversion approach

One of the most important goals in neuroscience and neuroengineering is noninvasive deep brain stimulation and imaging. Recently, lanthanide-doped upconversion nanoparticles (UCNPs) have been developed as a new class of optical actuators and labels to allow for the use of near-infrared light (NIR) to optogenetically stimulate and image neurons nestled in deep brain regions. Besides the high penetration depth of NIR excitation, UCNPs show advantages in neuronal imaging and stimulation due to their large anti-Stokes shifts, sharp emission bandwidths, low autofluorescence background, high resistance to photobleaching, high temporal resolution in photon conversion as well as high biocompatibility for in vivo applications. UCNP technology paves the way for minimally invasive deep brain stimulation and imaging with the potential for remote therapy. This review focuses on the recent development of UCNP applications in neuroscience, including UCNP-mediated NIR upconversion optogenetics as well as UCNP-assisted retrograde neuronal tracing and imaging.