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High impact publication for Synapse research

The team of Sander Groffen and Matthijs Verhage discover the mechanism for spontaneous release and published their results on Feb 12 in the online version of Science.

Spontaneous brain activity

According to current theory, the brain uses a mixture of electricity and chemistry to propagate signals to their destination. The electricity is especially important to propagate signals within a single nerve cell. When the signal arrives at a synapse (a contact point between nerve cells), a chemical signal is released in the form of neurotransmitters. The speed of this process is extraordinary. In less than a millisecond, the electricity causes a massive flow of calcium into the synapse. The calcium activates a protein, Synaptotagmin, which subsequently causes the release of neurotransmitters. This all can take place so fast because all the necessary components are held very close together even before any electrical signal occurs.

But the current theory does not explain everything we see. For example, you would think that nerve cells do not release neurotransmitters unless they receive an electrical signal. Wrong: they do it all the time. This phenomenon termed spontaneous release has been recognized for over 50 years, but the mechanism remained unclear.

Researchers in the Neuroscience Campus Amsterdam now discovered the mechanism for spontaneous release and published their results on Thursday in the online version of Science. The team of Sander Groffen and Matthijs Verhage collaborated with the research group of Sascha Martens and Harvey McMahon in Cambridge.

The mechanism is strikingly similar to that of conventional release, except that it uses Doc2b, a protein that is 100 times more sensitive than Synaptotagmin. Deletion of the Doc2b gene in mice caused abnormal nerve cell activity, indicating that spontaneous release contributes to overall brain activity.

This changes our understanding of brain function. So far, neuroscientists have focused much on conventional neurotransmitter release. It’s as if listening to a concert from the room next door: by hearing the loud percussion but not the soft strings, you don’t really get the complete picture.

The discovery makes it possible to start investigating the importance of spontaneous brain activity for various tasks performed by the brain, such as learning and memory. The researchers also started to investigate if genetic mutations in Doc2 may be involved in nervous system diseases.

See paper in Science