Light-activated ion channels for remote control of neuronal activity

old_uid1393
titleLight-activated ion channels for remote control of neuronal activity
start_date2006/06/09
schedule11h30
onlineno
summaryNeurons have ion channels that are activated directly by voltage, chemicals, and mechanical forces, and temperature, but not by light. Using a combination of organic chemistry and molecular biology, we have engineered the first neuronal ion channel that can be directly activated with light. A chemically synthesized "photoswitch" molecule is covalently coupled to genetically engineered ion channel protein. The photoswitch contains a ligand that binds to the pore of the channel, blocking the flow of ions. When the photoswitch is in its extended (trans) configuration, the blocker can reach the pore and the channel remains closed, but exposure to ultraviolet light triggers photoisomerization to the bent (cis) form of the molecule, retracting the blocker from the pore, and allowing ion flow. The photoswitch can be switched rapidly and repeatedly with different wavelengths of light, allowing precise and consistent control of channel opening and closing. Expression of these channels in neurons allows action potentials to be regulated with flashes of light. Light-activated channels could serve as "remote control" devices for non-invasive control of neural activity---an alternative to neural prosthetic devices based on implanted electrode arrays. One particularly intriguing target for these channels is in neurons of the retina---the one part of the nervous system that is naturally accessible to light. By converting "blind" retinal neurons (e.g. retinal ganglion cells) into artificially photosensitive cells, it may be possible to restore visual sensitivity to blind animals that have lost their natural photoreceptors (rods and cones) to injury or degenerative diseases.
responsiblesBrunel