Near-infrared Deep Brain Stimulation in Living Mice

Optogenetics has revolutionized the experimental interrogation of neural circuits in the past decade and holds potential for the treatment of neurological disorders. However, optogenetic stimulation of deep brain neurons requires the insertion of invasive optical fibers because the activating blue-green light cannot penetrate deep inside brain tissue. Here we describe a minimally invasive technique for the stimulation of deep brain neurons by transcranial near-infrared light (NIR), where upconversion nanoparticles (UCNPs) are used as optogenetic actuators to locally convert NIR into visible light. We detail the protocol to use locally injected UCNPs to stimulate dopamine neurons in the ventral tegmental area (VTA) of anesthetized mice by transcranial NIR.