AsianScientist (Jun. 27, 2017) – In a study published in eLife, researchers from the Okinawa Institute of Science and Technology Graduate University (OIST) have discovered the factors controlling the flow of neurotransmitters in the pre-synaptic terminal. Their findings shed light on neurological disorders where communication at the synapses has been disrupted, such as anxiety and schizophrenia.
While the of transmission of information at the contact point between two neurons—the synapse—has been thoroughly studied, the transportation of this information within the terminal end of the neuron, called pre-synaptic terminal, remains relatively uncharted waters. In the pre-synaptic terminal, neurotransmitters are picked up and carried within cellular bubble-like ‘vehicles’ called vesicles.
“How do these vesicles move around and what does vesicle traffic look like within a synapse? And which kind of factors could regulate their motion and explain the wide range of vesicle mobility observed among synapses?” wondered Dr. Laurent Guillaud, OIST researcher and author of the study.
The movement of synaptic vesicles is thought to be random. However, Guillaud’s research shows that the phenomenon is actually much more complex. In fact, their study showed that the mobility and dynamic properties of these vesicles within the pre-synaptic terminal relied strongly on two factors: the type and size of the synapse, and the composition of the vesicle itself.
“Conventional synapses are those tiny buttons, down to one or two microns [one millionth of a meter], and it makes it really hard to observe the movement of vesicles in such a small space,” said Guillaud. “Instead we used ‘giant synapses,’ originally found in the central auditory system, which are 20 times larger and that we successfully grew in Petri dishes for our real-time imaging experiments.”
The researchers used an antibody linked with fluorescent tags to track the movement of vesicles within the giant synapses. Using algorithms to track a large number of vesicles simultaneously, the researchers discovered that the vesicles’ motion is not entirely random. A wide range of movements takes place inside the synapse, with different speeds, distances and directionalities.
Once the technique was validated in the giant synapses, the researchers expanded the study to compare the motion of these vesicles across smaller synapses. They discovered that the size of the synapse also has a direct impact on the direction and speed of the vesicles.
“Recently, physical factors such as hydrodynamic interactions, crowdedness and collisions have been reported to influence vesicles mobility, but there is very little data on biological factors determining vesicle dynamics. What we showed here is that the type of synapse, its structural organization and its morphology are critical factors influencing the motility of the vesicles,” Guillaud added.
A public transportation system loses efficiency if the vehicles stall or are stuck in traffic jams. Similarly, in the pre-synaptic terminal, vesicles unable to carry neurotransmitters might be the cause of neuronal diseases. Therefore, the ability to track these vesicles might reveal important clues.
“In neurodegenerative diseases, there are often issues of impaired transmission of information through the synapse. It might be due to problems with releasing neurotransmitters, but it might also be because vesicles movements are somehow impaired inside the pre-synaptic neuron,” said Guillaud.
“It would be particularly interesting to check whether vesicles move normally within the synapses in neuro-pathological disorders. And if not, how we can fix the traffic issues! But first, we need to identify and understand the mechanisms that correlate the morphological features of the synapse and the molecular signature of vesicles with their dynamic properties and movements.”
The article can be found at: Guillaud et al. (2017) Presynaptic Morphology and Vesicular Composition Determine Vesicle Dynamics in Mouse Central Synapses.
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Source: Okinawa Institute of Science and Technology Graduate University.
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