
- 报告摘要
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Technologies to modulate neural circuit function is not only critical for understanding how the brain generates behaviors but also important for treating brain disorders. Recently, several new technologies, such as electric field-based temporal interference and nanomagnetic particle-based neuromodulation for minimally invasive neuromodulation. However, these technologies lack cell-type-specificity, critically important for dissecting neural circuit function and dysfunction. To fill this gap, we engineered a new super-sensitive optogenetic tool for precise neural modulation with minimal invasiveness. Optogenetics is among the most widely employed techniques to manipulate neuronal activity. However, a major drawback is the need for invasive implantation of optical fibers into the brain. To develop a minimally invasive optogenetic method that overcomes this challenge, we engineered a new step-function opsin with ultra-high light sensitivity (SOUL). We show that SOUL can activate neurons located in deep mouse brain regions via transcranial optical stimulation and elicit behavioral changes in SOUL knock-in mice. Moreover, SOUL can be used to modulate neuronal spiking and induce oscillations reversibly in macaque cortex via optical stimulation from outside the dura. By enabling external light delivery, our new opsin offers a minimally invasive tool for manipulating neuronal activity in rodent and primate models with fewer limitations on the depth and size of target brain regions and may further facilitate the development of minimally invasive optogenetic tools for the treatment of brain disorders.