Neurosciences: a Protein Optimizes the Synaptic Signal
Prof. Ralf Schneggenburger's research group has made a step forward in understanding signal transmission in neuronal networks, thanks to new methods to molecularly influence the nerve terminal. Their innovative approach has been described in two consecutive articles in Neuron and may lead to new research methods for the neurosciences...
Neurons communicate with each other at synapses through complex mechanisms. The synapses establish contact between the neurons and convert their electrical signals into chemical signals, the release of neurotransmitters. Study of these phenomena is one of the essential keys to understanding the brain. The team from the EPFL’s Laboratory of Synaptic Mechanisms, headed by Ralf Schneggenburger, has shed some light on previously unknown functions of proteins in the release of neurotransmitters.
In the first paper (1), the researchers demonstrated that it was possible to deactivate a protein selectively in the calyx of Held, the brain’s largest synapse. This novel method enabled them to discover a direct, unexpected role for the protein RIM (Rab3 interacting molecule), which increases the density of calcium ion (Ca2+) channels, a type of ion channel that plays an essential role in neurotransmitter release.
In the second article (2), the scientists used mice that had been genetically modified so they would not produce a specific protein, synaptotagmin. This Ca2+-sensing protein is known to bind calcium ions (Ca2+), thus initiating neurotransmitter release. The researchers used a virus to reintroduce the missing gene in the nerve terminal and reestablish the gene function at the calyx of Held.
A Protein’s Double Life
Subsequently, the scientists used viruses expressing slightly modified versions of the gene coding for the protein. Careful comparison enabled them to reveal a double role of this protein. The function of synaptotagmin is in fact not limited to initiating neurotransmitter release; it also inhibits other Ca2+- sensing proteins present in the nerve terminal. In doing so, it increases the amplitude of the release signal while suppressing background release events. In other words it optimizes the signal quality, similarly to what occurs in an electronic circuit.
The approaches developed by Ralf Schneggenburger’s team are promising. They should also help us gain more insight into the function of other proteins that are active in the synapses. Since synaptic transmission is the basis of all fast communication between neurons in the brain, misfunction at synapses can underlie several neurodegenerative- and psychiatric disorders of the brain, including Alzheimer's Disease. "Therefore, a better understanding of the molecular bases of synapse function will contribute to the development of treatment strategies of these disorders in the future,” the researcher explained.
(1)Neuron, January 27, 2011, “RIM determines Ca2+ channel density and vesicle docking at the presynaptic active zone”
(2)Neuron, February 24, 2011, “Synaptotagmin increases the dynamic range of synapses by driving Ca2+ - evoked release and by clamping a near-linear remaining Ca2+ sensor”
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