Individual-neuron optical brain stimulation (iOBS) alleviates behaviors in an Alzheimer's disease mouse model

Stimulating cortical neurons through multisensory inputs or deep brain neurons via invasive electrodes has been found to alleviate the pathology and behavioral symptoms of Alzheimer's disease (AD). The activation of neuronal firing helps to initiate the neuronal repair process and improve memory and synaptic growth. In this study, we report an optical noninvasive method, termed individual-neuron optical brain stimulation (iOBS), to stimulate individual neurons in the cortex using a tightly focused femtosecond laser that transiently scans in a microdomain of each targeted neuron for a flash by two-photon excitation of the intrinsic flavin there. The stimulation activates intense Ca2+ activities of neurons at layer 5/6 in the brain cortex. We demonstrate that iOBS works effectively in the AD mouse model. By performing iOBS in ∼60 randomly selected individual neurons in the visual cortex for a single time, the behavioral symptoms of AD mice are significantly alleviated via the initiation of the neuronal repair process. This method provides a direct and noninvasive method of brain stimulation with promising potential for AD treatment.