Nerve Cells Controlled via Light Pulses

Using channelrhodopsins — ultralight-sensitive membrane proteins that can be inserted into cell membranes — researchers now can precisely control nerve cell activity with weak light pulses.

Because channelrhodopsin has a slightly increased calcium permeability, the protein variant CatCh (calcium translocating channelrhodopsin) can trigger nerve impulses with seventyfold less light and with greater precision and speed than other forms of the protein. This allows for the light stimulation of cells located in deeper brain regions without the need for additional optic fibers. Moreover, sunlight can be used instead of laser light to stimulate the cells, which means the new molecule presents a promising tool for possible use in clinical applications to treat individuals suffering from diseases such as epilepsy, Parkinson’s or blindness.

Neuron from the mouse hippocampus. The cell expresses the highly sensitive channelrhodopsin CatCh. It is visualized with the help of a fluorescent dye. (Image: Max Planck Institute for Biophysics)

A research group led by Ernst Bamberg at Max Planck Institute for Biophysics has reported that, when the nerve cell is exposed to light, positively charged ions flow through the channel protein into the cells, so that the cell’s interior becomes positively charged, triggering an electrical signal.

"CatCh opens up a whole palette of new possibilities, thanks to its high sensitivity to light," said Sonja Kleinlogel, first author of the study. "It allows us to control cells located in deeper brain regions without the need to transmit the light pulse to these areas using optic fibers. Moreover, the possibility to use longer wavelengths of light or reducing the light power to activate CatCh prevents tissue damage, which is an issue when stimulating other channelrhodopsins with strong laser light."

And because of its fast response kinetics, the new channelrhodopsin also enables the control of cells that intrinsically fire at higher frequencies, such as the hair cells in the inner ear or some interneurons in the cortex. This combination of high light sensitivity with a fast response time is unique and does not exist in any other variant of the channelrhodopsin protein.

Channelrhodopsin originally was isolated from the unicellular green algae Chlamydomonas rheinhardtii. As a component of their cell wall, it enables the algae to respond to light. Since its discovery in 2003, also in Bamberg’s research group at Max Planck Institute, the channelrhodopsins have become an important tool in cell and neurobiology and have revolutionized brain research. For the first time, nerve cells can be controlled without the use of electrodes and with unmatched temporal and spatial precision. Thus, the molecular activity switches are not only indispensable tools to unravel the functional connectivity of the brain, but also bear a huge potential for future clinical, genetherapeutic applications. For example, they could be used to treat blindness caused by the loss of photoreceptors. Patients with diseases such as epilepsy or Parkinson’s may also profit from these “light switches.”

"Normal sunlight already suffices to activate CatCh and thus excite nerve cells," Kleinlogel said. "The event of CatCh moved optogenetics a big step forward into the direction of clinical treatments."

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