RATS with breathing problems caused by damage to their nerves have had normal breathing restored by bursts of visible light aimed onto the spinal cord. This achievement raises hopes that a miniature light source implanted near the spine might one day allow people with similar injuries to breathe normally.
In 2005, Ed Boyden at the infected neurons in Petri dishes with viruses carrying the ChR2 gene, which codes for a light-sensitive protein called channelrhodopsin-2. The neurons started expressing the protein, and this allowed the researchers to to control when the neurons fired (Nature Neuroscience, vol 8, p 1263). 鈥淭he nerve cells think they are photoreceptors,鈥� says neuroscientist at
in Cleveland, Ohio.
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Silver has now taken things a step further with a study to investigate how this light-operated neuronal switch might be used to restore function lost as a result of nerve damage. His team cut part way through the spinal cords of rats at the second vertebra from the top, where the neck pivots, severing the connection between the spinal cord and the nerves that control one side of the diaphragm. This prevented messages from the brain getting to the diaphragm, leaving the animals with problems breathing. Similar injuries are the leading cause of death in people with spinal cord damage.
The researchers then injected a virus containing ChR2 just below the injury. Four days later they cut into the animals again to expose the spinal cord and shone light onto the damaged section. A 1-minute sequence of half-second pulses produced some activity in the neurons, and consequently in the damaged side of the diaphragm.
The big breakthrough came when they extended the treatment to three 5-minute cycles of 1-second light pulses followed by 5 minutes of rest. 鈥淎 bizarre seizure activity started,鈥� says Silver. When the seizure ended, normal breathing resumed and lasted for about a day and a half (, ). Surprisingly, the two sides of the diaphragm were working in tandem.
In uninjured animals, the two sides are synchronised by the brain 鈥� raising the question of how they could remain in sync when the nerve to one side was still severed. Silver reckons that in his rats, the light activates a latent network of neurons that span the spinal column, allowing the two sides to communicate independently of the brain.
Boyden sees Silver鈥檚 discovery as a powerful proof of principle. 鈥淚t opens up the investigation on how you can recruit existing circuits to compensate for lost ones.鈥�
Silver says the light-switch technique could one day be used to treat people with breathing problems resulting from nerve damage. Patients could be given an implant that would shine light on damaged nerves, eliminating the need for repeated surgery.
鈥淧atients with breathing problems could one day be given an implant that would shine light on damaged nerves鈥�
A similar device might be used to relieve constriction of the bladder caused by nerve damage. Boyden is working on a device that would achieve this without the need to surgically expose the neurons. Samarendra Mohanty at the in Irvine, California, is developing an infrared light source that can be piped into nerves through fibres about 50 micrometres thick, also with the aim of activating nerves remotely.
