Fiber Photometry with Tapered Optical Fibers: Exploiting Mode-Division to Gain Depth-Resolution in Brain Tissue

Fiber photometry is an emerging technique enabling the monitoring of neural activity in vivo by employing optical fibers to detect functional fluorescence variations from specific genetically-encoded indicators expressed in neurons. It benefits from an ever-growing number of fluorescent indicators and it is considered a valuable tool in the field of neuroscience for investigating neural circuits underlying behavior and disease. Fiber photometry is typically performed by implanting an optical fiber or a fiber bundle in the region of interest, allowing the propagation on the same optical channel of both the excitation light and the functional fluorescence signal. However, conventional cylindrical fibers lack spatial resolution and can cause brain damage upon insertion. An alternative solution employed in fiber photometry are Tapered Optical Fibers (TFs), which allow for a smooth insertion and reconfigurable light delivery and collection for a depth which can easily reach subcortical structures of the mouse brain. In this manuscript we review the latest applications of TFs in the context of fiber photometry, discussing their light delivery and collection capabilities, the advantages offered by the microstructuring of the taper edge, and the unique possibility to detect fluorescent signals from multiple brain depths simultaneously with a single implant.