High-density microfibers as a potential optical interface to reach deep brain regions.

Objective. Optical techniques for recording and manipulating neural activity have traditionally been constrained to superficial brain regions due to light scattering. New techniques are needed to extend optical access to large 3D volumes in deep brain areas, while retaining local connectivity. Approach. We have developed a method to implant bundles of hundreds or thousands of optical microfibers, each with a diameter of 8 mu m. During insertion, each fiber moves independently, following a path of least resistance. The fibers achieve near total internal reflection, enabling optically interfacing with the tissue near each fiber aperture. Main results. At a depth of 3 mm, histology shows fibers consistently splay over 1 mm in diameter throughout the target region. Immunohistochemical staining after chronic implants reveals neurons in close proximity to the fiber tips. Models of photon fluence indicate that fibers can be used as a stimulation light source to precisely activate distinct patterns of neurons by illuminating a subset of fibers in the bundle. By recording fluorescent beads diffusing in water, we demonstrate the recording capability of the fibers. Significance. Our histology, modeling and fluorescent bead recordings suggest that the optical microfibers may provide a minimally invasive, stable, bidirectional interface for recording or stimulating genetic probes in deep brain regions-a hyper-localized form of fiber photometry.