Optically Selective Neuron Stimulation with a Wavefront Shaping‐Empowered Multimode Fiber

TLDR

Optogenetics enables exploration of neural circuits, yet scattering in tissue limits depth and resolution, and bulky GRIN lens microendoscopes, while improving confinement, cause tissue damage. The authors use an ultrathin multimode fiber combined with optical wavefront shaping to focus and rapidly raster‑scan light at the fiber tip, enabling precise neuron stimulation without mechanical motion and even through a mouse skull. Using this approach, primary neurons expressing Chr2 were spatiotemporally regulated, suggesting that the technique could enable noninvasive or minimally invasive all‑optical interrogation of neural circuits in previously inaccessible brain regions.

Abstract

Optogenetics is proved to be a powerful tool for exploring the connection between behavior and neural circuits. The progress greatly benefits from the advances of optical techniques that enable high spatiotemporal resolution for selective single‐neuron stimulation through modulating light. Efficient propagation of modulated light, however, is handicapped by strong optical scattering in biological tissues, which results in inherent tradeoff between penetration depth and resolution. Schemes like graded index (GRIN) lens‐based microendoscopes are developed to yield more confined delivery of light, but tissue damage caused by the insertion of the bulky components cannot be ignored. Herein, an optically selective precise neuron stimulation using an ultrathin multimode fiber (MMF) is demonstrated, which is empowered by optical wavefront shaping to achieve light focusing and rapid raster scanning without mechanical movement at the distal end of the MMF and even through a mouse skull. With this method, primary neurons expressing Chr2 can be regulated spatiotemporally in experiment. Although a lot shall be further improved, the work may open up new venues for noninvasive or minimally invasive all‐optical investigation of neural circuits in used‐to‐be optically inaccessible brain regions.