New light-controlled tool allows gentle and precise silencing of neurons

A research team involving several MPINB scientists, including former PhD student Nidish Ponath Sadanandan, Wolfgang Bönigk, and Reinhard Seifert has contributed to the development of a new optogenetic tool called RoCK. This method uses light to gently silence nerve cells in a way that more closely resembles natural brain processes.

Why silence neurons with light?

To understand how the brain works, scientists often need to switch nerve cells on or off in a temporally and spatially controlled way. Light-based tools are perfect for this because they can target very specific cells without affecting their neighbors. However, switching cells off has long been challenging. Many existing tools change the ion balance in a way that cells rarely experience in nature.

A more “natural” way to switch neurons off

RoCK takes a different approach. It uses:

• a light-sensitive protein that produces a messenger molecule (cGMP), and
• a potassium channel that was engineered to open specifically when this messenger is present.

Potassium channels normally support the resting state of neurons. When RoCK is activated, neurons become quieter, similar to how the brain naturally stabilizes activity. This makes RoCK a gentle and physiologically grounded method for temporarily calming cells.

What makes RoCK special?

RoCK offers several advantages:

• Fast response: It reacts within milliseconds to green (or even red) light.
• Precise control: Researchers can fine-tune how strongly cells are silenced.
• Low background activity: The system stays quiet in the dark, reducing unwanted effects.
• Modular design: The two components can be adapted for different experimental needs.

Tested in neurons, heart cells, and living animals

The tool worked reliably in several systems:

• Mouse neurons: Brief light pulses could silence neuronal activity for several seconds.
• Heart muscle cells: RoCK silenced or shortened action potentials without disturbing the resting state of the cells.
• Zebrafish embryos: In living animals, RoCK quickly and reversibly silenced motor neurons, stopping the characteristic “coiling” movement.

Why this matters

RoCK adds an important new option to the growing optogenetic toolbox. With its high precision and gentle mode of action, it will help researchers explore how neural circuits control behavior, one of the central scientific goals at MPINB.

Contribution from MPINB

At MPINB, Nidish, Wolfgang, and Reinhard developed and optimized the cGMP-gated channel which is a central element of RoCK.

Read the full publication here.