Optogenetics and Neuroprosthetics Combine

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Optogenetics is a very young field of study in direct brain interfaces. Only a handful of years old, it combines genetic trait knowledge with optical, non-invasive probing in order to decode neural circuitry in mammalian brains, in real-time. However, usually it is used with genetically altered neurons, as neurons are not naturally sensitive to light.

That technique may be no-longer necessary, or at least, limited in lifespan. A new effort combines optogenetics with synthetic biology. Specifically, the researchers use an artificial compound to sensitize select types of cells in the brain to a particular colour of light. This has been done with gene therapy applied to living mice, so the technique can alter the genetics of existing living creatures to be compatible. Of course, as is usual with the brain, if it works on mice, it'll work on people. Our brains are remarkably similar in composition to theirs.

The molecules used in the synthetic compound are opsins, light-detecting proteins naturally found in algae and bacteria. Genes for an opsin are transferred to the neurons in a mouse's brain using gene therapy, a process in which DNA is ferried into a cell via a carrier such as a harmless virus. The carrier can be instructed to deliver the DNA package only to certain types of cells.

This delivery method to certain types of cells is key. It means the delivery can be targeted to certain types of neurons only; leaving others unaffected. In addition other cells in the brain that are involved in the cogitation process, such as the gila cells, remain completely unaffected by the process.

Once the therapy has made the necessary changes, its time for the neuroprosthetics to come in, and connect to the newly light-sensitive cells. The method of neuroprosthetics pioneered by the BrainGate prosthesis is used here, with an array of hundreds of probes arranged in a three-dimensional grid, on the surface of a single microchip which is carefully implanted into the target area of the brain.

This is an optical image of the 3-D array with individual light ports illuminated. The array looks like a series of fine-toothed combs laid next to each other with their teeth pointing in the same direction.
Credit: A.N. Zorzos, J. Scholvin, E.S. Boyden, and C.G. Fonstad/Optics Letters.

Unlike the original BrainGate array, which detected electrical impulses, and read the thought patterns, the optogenetic array is a writer. It lights up in patterns which activate nearby neurons and trigger a response. Unlike normal deep brain stimulators, which have to emit a blanket pulse, the light-based method will only target neurons in the immediate vicinity of each pulse of light. So they don't drown out any other devices that are trying to read the electrical signals produced. For the first time then we have a very real possibility of two-way communication between a mind and a 'mind reading' computer interface.

Further, the light-based interface does not suffer the one key problem the BrainGate interface has always had: The trauma of inserting the device, however gently and carefully into the brain, triggers the build up of scar tissue around the wound. The brain lacks pain receptors, so the implants do not cause any discomfort to the brain itself, but natural bodily responses to damage still proceed as normal..

As this scar tissue thickens over a matter of months, it effectively insulates the array from the cells it is trying to communicate with. When you switch from electricity to light, you no-longer have this problem, and the build-up of scar tissue does not inhibit the functioning of the prosthetic.

In basic terms, the effective 18-month lifespan of an embedded neuroprosthetic in a living brain, no-longer exists.

Each optogenetic probe in the array, is also much smaller than the 1mm electrodes used in the first implanted arrays. Each optic probe is just 150 microns across – a little thicker than a human hair. Each has a dozen light-emitting ports up and down its length, allowing a three-dimensional light field to be generated within the target area.

The individual ports can be controlled separately, so researchers using the implant can precisely control the 3D pattern the implant puts out. That is ideal, given the purpose of such implants: To help us reverse engineer the neural codes the brain uses to communicate internally. Once we understand the programming language and procedure calls the brain makes as standard, then things become a lot more interesting, and the capabilities of such implants increase dramatically.

Neural code reverse engineering has been in full swing in other areas as well. In the peripheral nervous system, the reverse engineering of neural codes has allowed us to create prosthetic arms and legs that respond to instinctual movement commands from the brain, sent down the old nerve pathways. The limb then moves without conscious thought. Likewise, by understanding what the neural codes for different touch nerve endings are, we are now able to replicate them, and give a sense of touch back to users of prosthetics. When a high-grade modern prosthetic hand touches something, the wearer can feel the pressure against their fingers, just as they could with the original hand.

So reverse engineering the codes of the brain itself will allow us to accomplish something similar, but much more profound: To be able to communicate with the brain, just as the body does. To be able to take control of all sensory input and output, should we need to. Everything from the elimination of many disabilities, to Matrix-style brain-jacks becomes feasible once we understand the codes.

This is a scanning electron microscope image of the 3D array with closeup of a single light-emitting probe. The closeup reveals several light ports along the probe's edge.
A.N. Zorzos, J. Scholvin, E.S. Boyden, and C.G. Fonstad/Optics Letters.

For now, the goals are of course, much more modest. Simply unlocking the codes that underlay all our autonomic processes, is the goal unto itself.

The currently used arrays also have the option to show different colours, again linked to the functioning of the opsins in the gene therapy. By including a more complex range of opsins, a more powerful communicating ability has opened up – different colours provoke different responses.

Specifically, blue might cause one opsin to activate a cell, while yellow might cause another opsin to silence it.

The response of an individual neuron – whether to turn on or turn off – depends on the type of opsin it was sensitized with, and the colour of light used to illuminate it. In this way, the tool gives neuroscientists an unprecedented level of control over individual neurons in the brain.