Questions like these might now become easier to address: Scientists at the University Medical Center Hamburg-Eppendorf (UKE) and Humboldt University in Berlin have created a novel molecular switch that could be a valuable new tool for brain research.

The new findings of Prof. Thomas Oertner, Prof. Peter Hegemann and their coworkers have just been published in the journal “Science”.

“We inverted the ion selectivity and turned an excitatory channel into an inhibitory one”, explains Prof. Thomas Oertner, director of the Institute for Synaptic Physiology at the Center for Molecular Neurobiology Hamburg (ZMNH). “We were astounded to discover, that a single point mutation – changing a single letter of the genetic code – could be sufficient to completely invert the sign of current flowing through this channel. We also demonstrated that nerve cells can be selectively switched off with our new tool.”

This finding opens up new possibilities for basic research. Thomas Oertner and his team, for example, are planning to use this tool to investigate emotional aspects of learning. It is also conceivable that this channel could be used to dampen the activity of affected brain regions during epileptic seizures.

From algae to brain research – the emerging field of Optogenetics

Channelrhodopsins are proteins that are activated by light, allowing electrically charged ions to pass through biological membranes. Opening these channels changes the voltage across the membrane. In this way, nerve cells can be tuned on or shut off by light. Channelrhodopsins were discovered in unicellular green algae, which use them to swim towards light.

The biophysicist Prof. Peter Hegemann at Humboldt University in Berlin is credited with the discovery of channelrhodopsin, laying the foundation for the new field of optogenetics. With this latest discovery, optogeneticists have a completely new set of tools at their disposal: One of the new proteins, the chloride-conducting channelrhodopsin with slow kinetics or ‘slow ChloC’, opens its pore and shuts off neurons for several seconds after a short flash instead of needing constant light like the older inhibitory tools. “This means, we now need ten thousand times less light to block neuronal activity”, explains Thomas Oertner.

The research project at the UKE was supported by the German Research Foundation (DFG).

Literature:
Wietek J, Wiegert JS, Adeishvili N, Schneider F, Watanabe H, Tsunoda SP, Vogt A, Elstner M, Oertner TG, Hegemann P (2014). Conversion of Channelrhodopsin into a light-gated chloride channel. Science, March 27, 2014. http://www.sciencexpress.org

Contact:
Prof. Dr. Thomas G. Oertner
Institute for Synaptic Physiology
Center for Molecular Neurobiology Hamburg (ZMNH)
University Medical Center Hamburg-Eppendorf (UKE)
Falkenried 94
D-20251 Hamburg
Germany
Phone: +49 (40) 7410-58228
E-mail: thomas.oertner@zmnh.uni-hamburg.de