Optics links brain research to behavior

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Optics and microscopy have always played important roles in neuroscience. The innovations brought by optogenetics and fiber photometry, in the context of freely moving animals and behavioral research, have only reinforced those roles. Conventional microscopy has been complemented by imaging of individual neuronal activity within a selected group of tagged neurons by a miniature fluorescent microscope, or miniscope, mounted directly on the heads of freely moving, tethered lab animals.

Miniscopes and fiber photometry, combined with optogenetics, provide the basis for modern behavioral neuroscience studies. There is now even a word — “neurophotonics” — coined to refer to the use of photonic devices and light in neuroscience. The future of behavioral neuroscience lies in the convergence or fusion of optogenetics, genetically encoded indicators, fiber photometry, various forms of microscopy, and good old electrophysiology.

As I sit at the helm of Doric Lenses Inc., my job is to anticipate the future need for neurophotonic hardware and accordingly redirect the company’s research and development efforts. I do this by analyzing sales reports and by sifting through a pile of requests coming from some of the most famous and not-sofamous neuroscience institutions around the world.

From what I have seen, behavioral research is still dominated by freely moving, tethered animals. These experiments in which they appear need light and electrical signal sources, rotary joints, electrical and optical cords, liquid tubing, detectors, and skull-mounted one-site or multisite brain interfaces in the form of simple fiber optic cannulas or hybrid implants.

Optogenetics equipment has matured and gained general acceptance. The new light-sensitive opsins require precise light sources that take into account the size of emitters, the ease of signal modulation, and the activation spectrum. The market of brain interfaces — which is a trendy name for all sorts of fiber optic and hybrid cannulas, electrical implants, and head stages as ports of entry to the brain — requires never-ending diversification in types and geometries.

Fiber photometry equipment that was initially very modular, with detectors and light sources connected to fluorescent cubes with optical fibers, is slowly being replaced by more compact cubes in which detectors and LED light sources are attached directly to the cubes. The elimination of unnecessary optical fibers improves the signal-to-noise ratio and makes the setup more user-friendly. Consequently, neuroscientists can spend less time fiddling with the equipment and more time doing experiments. Multisite fiber photometry and CMOS and sCMOS detectors are becoming increasingly popular. Many electrophysiology companies are embracing fiber photometry as a complementary sensor to their existing equipment.

Miniscopes are gaining more acceptance as their design improves and researchers learn to master cannula implantation. The varifocal objective is becoming a norm rather than an option. Adding two-fluorophore imaging to head-mounted fluorescence microscopy, or combining fluorescence microscopy with optogenetics or electrophysiology, is becoming more common.

The larger picture of neuroscience

Although neuroscientists are using various brain interfaces to study the brain’s functions and malfunctions on the lab animal level, the ultimate goal is understanding the inner workings of the human brain. They hope to begin repairing its ills and creating a direct communication channel between the human brain and the computer, machine, or parts of the body that have lost their natural connections to the brain. It is not a question of if it will happen on a larger scale, but when it will happen. As I write this column, the news is out about Elon Musk’s Neuralink brainmachine interface development. So far, this interface, which has generated a lot of hype, does not involve humans or optics, but that will change sooner rather than later.

Unlike almost universal government support for university neuroscience research, there is a very little direct government support for neurophotonic hardware development (at least in Canada where I am based). This industry, consisting of relatively small niche companies, lives off proceeds from sales of equipment to the less-regulated lab-animal-level neuroscience research market. To get through development, FDA approvals, clinical trials, and distribution channels, neurophotonic hardware for human use will require government programs (such as those of the National Institutes of Health), venture capital involvement of the Elon Musk type, or acquisitions of niche players by larger health care companies.

In the meantime, the existing neurophotonics industry is preparing itself for that “human phase” by sharpening its tools with whatever profits it can generate through sales to the lab animal research market. This is vast uncharted territory with a huge disruptive potential. Neurophotonics is entering a phase of rapid and rewarding growth — and the photonics component of that movement should not be underestimated.

Meet the author

Sead Doric, Ph.D., physicist by profession, is founder and CEO of Doric Lenses Inc. As a researcher, he has published several scientific papers on gradient index optics and holds a number of optics-related patents. As an entrepreneur and engineer, he leads or participates in development of many Doric Lenses products.

The views expressed in ‘Biopinion’ are solely those of the author and do not necessarily represent those of Photonics Media. To submit a Biopinion, send a few sentences outlining the proposed topic to [email protected]. Accepted submissions will be reviewed and edited for clarity, accuracy, length, and conformity to Photonics Media style.

Published: October 2019

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