Interfacing with the nervous system: Studies in mice and rats show the way.

As fundamental scientific knowledge about how the nervous system works has increased over the past few decades, the possibility has emerged that we may one day be able to use electrical stimulation (or inhibition) to treat – even to functionally cure – conditions where it has been damaged by disease or injury.  Scientists are now working hard to make this dream a reality, indeed we have recently discussed the role of animal research in developing deep brain stimulation to treat Parkinson’s disease, and in the work being done to enable quadriplegic patients to operate robotic limbs, and even to restore voluntary control of their own limbs.

But these are not the only examples of how animal research is advancing the use of neural interfaces in medicine, today Nature News carries two articles on how groundbreaking research is paving the way for advances in optical prosthesis and the treatment of epilepsy.

Recent years have seen a number of innovative treatments for different types of blindness move from the lab to the clinic, including monoclonal antibodies, gene therapy and embryonic stem cells, Another approach that has been studied in patients for some time, and which may be useful in patients whose retina is too badly damaged to benefit from the techniques mentioned above,  is the use of neural prosthesis which replace damaged photoreceptor cells in the retina and directly stimulate the optic nerve, an approach discussed by Speaking of Research committee member Dario Ringach on his blog in 2010.

A prosthetic retina that can translate an image into neural signals was tested using a picture of a baby’s face. A is the original image. B is the image after it passes through the coding software. C is after it has been processed by the mouse retinal ganglion cells. D is the processed image without coding. Credit: Sheila Nirenberg, Nirenberg, S. & Pandarinath, C. Proc. Natl Acad. Sci. USA (2012).

Nature news reports that scientists at Cornell University have solved one of the greatest challenges facing this technology, how to encode the electrical signal so that the light hitting the prosthesis is turned into a signal that the brain can understand. This problem has meant that current retinal prosthesis only allow patients to discern edges or lines, but not to be able to see movement or recognize faces. Now Sheila Nirenberg and her colleagues report the development of a code that enables mice that are blind due to severe retinal degeneration to see with far greater acuity than was possible with earlier prosthesis, the Nature News article noting that:

After receiving the encoded input, the mice were able to track moving stripes, something that they hadn’t been able to do before. The pair then looked at the neural signals that the mice were producing and used a different, ‘untranslate’, code to figure out what the brain would have been seeing. The encoded image was clearer and more recognizable than the non-encoded one”

It’s an exciting discovery that combines advanced visual prosthetic technology – which converted the light into a pattern that the brain can understand –  and genetic modification to introduce the Channelrhodopsin-2 gene into the retinal ganglion cells of the optic nerve, thus enabling them to respond to the light pattern emitted by the prosthetic and pass it to the brain. They hope to take into clinical trials in the near future, and may well do so as variations on the techniques required for this approach – including gene therapy of the eye – are already well developed, and several have already proven successful when evaluated in human patients.

The second item in Nature news is a very interesting discussion of the potential to use of a different technology – transcranial electrical stimulation (TES) – to stimulate neurons using electrodes implanted in the skull of epilepsy patients. Deep Brain Stimulation has been used to treat patients with epilepsy who don’t respond to anti-epileptic drugs, but while it has proven to be effective in many cases its use has been limited by the risks inherent in the surgery required to implant the electrodes, and the side effects due to the electrodes being continually on.

In an article published this week in the journal Science, György Buzsáki and colleagues at the New York University School of Medicine reported the development of a TES implant that was able to detect epileptic seizures in rats and then turn on to limit the reduce the duration of the seizure. Dr. Buzsáki and his colleagues have so far only studies this technique in “petit mal” or absence seizures, and are now planning to study its effectiveness for other types of epileptic seizures, but the potential of an electrostimulation technique that can control epileptic seizures but requires less invasive surgery than DBS and turns on only when requires is great.

All in all, they are two articles that highlight both the advances being made in this field, and how those advances depend on animal research.

Paul Browne