Optogenetics: a revolution within every lab’s reach

For the inaugural OpenOptogenetics blog post, we would like to explore an issue that is central to this site’s existence: why the barriers to beginning an optogenetics project are low, and why a dedicated wiki can help keep them that way.

Optogenetics is a field with nearly unprecedented momentum, and for good reason. Optogenetic tools will become an increasingly vital part of researchers’ toolkits because they allow us to take a huge leap toward one of the primary goals of neuroscience: interacting with neural circuits in meaningful ways and on the timescale at which neurons operate. To facilitate the spread of these tools, and to ensure they are used effectively, we need to develop an open, centralized resource for sharing ideas with the whole neuroscience community. The major players in the field have already established a culture of openness (for example, see 1 and 2), but their techniques can still seem abstruse to prospective adopters. Even when reagents and protocols are made freely available, there are many steps between obtaining your first aliquot of ChR2 virus and running a successful experiment. We hope this wiki (and this blog) will make those steps easier and more affordable for everyone, no matter what their level of experience.

Gathering the right information

Because optogenetic tools were originally unfamiliar territory for every lab, the desire to employ them sparked many fruitful collaborations. Although the term “optogenetics” is a bit of a misnomer, as its application doesn’t involve any interaction between light and the genome [3], its etymology highlights the two areas that may be the most intimidating to the average neuroscientist. Many of the initial forays into optogenetics were made possible by collaboration between labs with a handle on molecular biology and labs focusing on in vivo electrophysiology and behavior (see references 4 and 5 for particularly successful examples). Advice from engineers with a background in optics helped more than a few projects get off the ground. Knowing the right people to talk to can save months to years of trial-and-error.

Establishing a new know-how with affordable bits and pieces

In addition to collaboration, a second feature of optogenetics research has been the need for homebrew equipment. Techniques for delivering genes to the brain may have been well-established, but those for delivering light to the brain were not. Because the molecular tools spread so quickly, commercial suppliers didn’t have time to bring any purpose-built hardware to market. In the early stages, every lab had to develop its own methods for light delivery, which ranged from cannulated optical fibers [6] to mounted LEDs [7]. As new techniques were developed, they spread by word of mouth. Both the authors of this post greatly benefitted from the hint that fiber optic ferrules, manufactured by Doric Lenses, were ideal for combining optogenetics with chronic electrophysiology. Today, a handful of suppliers are manufacturing optogenetics components, but they cannot yet match the flexibility or affordability of custom approaches. Many high-profile papers have been published using light-delivery systems that cost a minute fraction of the rest of the rig.

“Wiki-fying” optogenetics is very timely

Hunting for information on how to best implement simple optogenetic approaches made sense while optogenetics was burgeoning. But as the field is rising as tomorrow’s new standard, we shouldn’t let matters rest there. Sharing information is a necessary step toward reducing the barriers to adopting optogenetics.

Given the collaborative and “do-it-yourself” nature of the field thus far, a wiki-style website is the perfect forum for optogenetics. Not only can information be quickly distributed among labs, but researchers can also share helpful pointers and critical reviews of techniques and hardware. Such trade secrets are an important part of what makes an experiment successful, but are usually considered out of place in a peer-reviewed publication. Rather than being kept hidden, this information should be shared as widely as possible to become collective wisdom.

To be sure, the content of OpenOptogenetics.org is still sparse in some areas. But even in its current state, the available information would have been a godsend to its current contributors a few years back. There are instructions and parts lists for creating fiber optic ferrules, LED pigtailing and laser guidance, and hopefully more and more protocols will be posted to the site over the coming months. Out of the scores of the labs engaged in optogenetics research, only 7 have made significant contributions so far. So, if you have techniques that are working well, or ones you’d like feedback on, please post them on the wiki. With everyone’s input, we can minimize the costs of new experiments while maximizing their success rate.

Josh Siegle1 and Guillaume Dugué2

1: Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, MA, USA
2: Systems Neuroscience Laboratory, Champalimaud Neuroscience Programme, Portugal.

References

  1. The Optogenetic Resource Center.
  2. Protocols and Reagents of the Synthetic Neurobiology Group.
  3. Miesenböck G. 2009. The optogenetic catechism. Science 326:395-9.
  4. Adamantidis AR, Zhang F, Aravanis AM, Deisseroth K, de Lecea L. 2007. Neural substrates of awakening probed with optogenetic control of hypocretin neurons. Nature 450:420-4.
  5. Cardin JA, Carlén M, Meletis K, Knoblich U, Zhang F, et al. 2009. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature 459:663-7.
  6. Aravanis AM, Wang LP, Zhang F, Meltzer LA, Mogri MZ, et al. 2007. An optical neural interface: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology. J Neural Eng 4:S143-56.
  7. Huber D, Petreanu L, Ghitani N, Ranade S, Hromádka T, et al. 2008. Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice. Nature 451:61-4.
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