Demixing fluorescence time traces transmitted by multimode fibers.

Area of Science:

• Neuroscience
• Optical Engineering
• Biomedical Imaging

Background:

• Measuring deep brain activity in freely moving mice is challenging due to limitations of current optical methods.
• Fiber photometry offers only ensemble activity, while imaging with long multimode fibers is sensitive to bending and not suitable for unrestrained subjects.

Purpose of the Study:

• To develop and demonstrate a novel optical method for measuring deep brain neuronal activity using short multimode fibers (MMFs) coupled to miniscopes.
• To overcome the limitations of existing techniques for in vivo neuronal activity monitoring in deep brain regions.

Main Methods:

• Utilized a thin (200 µm) and short (8 mm) multimode fiber coupled to a miniscope.
• Applied an unconstrained non-negative matrix factorization algorithm to raw video data to disentangle spatio-temporal fluorescence signals.
• Validated the approach using in vitro proof-of-principle experiments with multiple fluorescent sources.

Main Results:

• Successfully disentangled spatio-temporal fluorescence signals from multiple sources transmitted through the short MMF.
• Demonstrated that low-cost, open-source miniscopes possess sufficient sensitivity for this application.
• Showcased the feasibility of imaging fluorescence patterns comparable to established methods.

Conclusions:

• The developed method offers a promising new avenue for minimally invasive deep brain studies in freely behaving mice.
• Short multimode fibers coupled with miniscopes provide a viable alternative for monitoring neuronal activity in deep brain regions.
• This approach enhances the potential for studying neural circuits in naturalistic behaviors.