Why some nerve cells have more to say

March 22, 2022

Nerve cells communicate via chemical neurotransmitters stored in small containers, termed synaptic vesicles. Some of these cells are more ‘articulate’ than others as they can send more than one type of messenger. By which mechanism such multilingual communication takes place, however, remained a puzzle. Researchers from the Max Planck Institute (MPI) for Multidisciplinary Sciences in Göttingen (Germany) have now determined the brain’s capacity to release distinct messengers at the same time. They showed that about a third of all vesicles in rodent brains can store and release distinct messengers.

Warm sun rays on the skin, music in the ears, or pain in the foot – our 86 billion nerve cells receive a lot of information. To ensure that the body can react to these inputs, the cells have to pass on the information correctly. As soon as a signal activates a nerve cell, the synaptic vesicles move to the cell’s outer membrane, merge with it, and release the neurotransmitters. These then travel to the receiving nerve cell. Depending on the type of neurotransmitter, it may trigger the cell to forward the signal or inhibit it from doing so.

“Co-release of distinct neurotransmitters by some nerve cells was already known. But whether these transmitters are released from the same pool of vesicles was an unresolved debate,” explains Sivakumar Sambandan, a project group leader in the Laboratory of Neurobiology Emeritus Group at the MPI for Multidisciplinary Sciences.

The majority of synaptic vesicles speak only one language

To answer this question, the researchers used advanced microscopy techniques to analyze the transporter proteins located on synaptic vesicles. These molecules pump and store neurotransmitters into the vesicles. The various types of neurotransmitters are thereby handled by different transporters. Not least due to the MINSTED microscopy developed by Nobel laureate Stefan Hell, the team was able to observe individual vesicles, which are 2,000 times smaller than the diameter of a human hair, under the microscope and identify their transporters.

“We discovered vesicles, which carried more than one type of transporter”, the biologist states. “Now we know for sure that multi-neurotransmitter vesicles exist in the brain but they are the minority.” One-third of all synaptic vesicles in rodent brains had two distinct transporters, each specified for one kind of neurotransmitter. Altogether, the team identified 27 types with different combinations of transporters. “This diversity was surprising and will keep us busy for some time”, observes Reinhard Jahn, who heads the Emeritus Group Laboratory of Neurobiology.

Multilingualism benefits not only humans but also nerve cells

Among the multi-neurotransmitter vesicles, the major part contained glutamate and zinc transporters. “Glutamate is the major and ubiquitous neurotransmitter involved in every type of neuronal communication. The discovery of the live-in relationship between glutamate and zinc transporters came to us as quite a surprise,” Sambandan says. As it turned out, zinc helps in the packing and storage of glutamate in synaptic vesicles. The more glutamate is stored in the vesicles the stronger are the nerve signals. As our body cannot synthesize zinc but must take it with our food, the researchers believe that this study will expand future investigations into the role of zinc in nerve function and mental health. (Sivakumar Sambandan, kr, cr)

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