Only a small portion of synapses, the connections between cells that control brain activity,  may be active at any given time, according new findings from Columbia University scientists. The team developed a new optical technique to study how information is transmitted in the brains of mice which led to the discovery.

David Sulzer, PhD, professor of neurobiology in Psychiatry, Neurology, and Pharmacology at Columbia University Medical Center (CUMC), said:

“Understanding how we accomplish complex tasks, such as learning and memory, requires us to look at how our brains transmit key signals, called neurotransmitters, across synapses from one neuron to another. Older techniques only revealed what was going on in large groups of synapses. We needed a way to observe the neurotransmitter activity of individual synapses, to help us better understand their intricate behavior."

To obtain a detailed view of synaptic activity, Sulzer’s team collaborated with the laboratory of Dalibor Sames, PhD, associate professor of chemistry at Columbia, to develop a novel compound called fluorescent false neurotransmitter 200 (FFN200). When added to striatum brain tissue or nerve cells from mice, FFN200 mimics the brain’s natural neurotransmitters and allows researchers to spy on chemical messaging in action.

[caption id=“attachment_26039” align=“aligncenter” width=“640”]synapses Credit: Sulzer lab/Columbia University Medical Center[/caption]

Using a fluorescence microscope, the researchers were able to view the release and re-uptake of dopamine— a neurotransmitter involved in motor learning, habit formation, and reward-seeking behavior— in individual synapses.

When all the neurons were electrically stimulated in a sample of brain tissue, the researchers expected all the synapses to release dopamine. Instead, they found that less than 20 percent of dopaminergic synapses were active following a pulse of electricity.

“Why are there these large reservoirs of synapses that are silent?” asked Dr. Sames, a co-author of the paper. “Perhaps these silent terminals hint at a mechanism of information coding in the brain that’s yet to be revealed."

The study’s authors plan to pursue this hypothesis in future experiments, as well as examine how other neurotransmitters behave.

“This particular study didn’t explain what’s causing most of the synapses to remain silent,” said Dr. Sulzer. “If we can work this out, we may learn a lot more about how alterations in dopamine levels are involved in brain disorders such as Parkinson’s disease, addiction, and schizophrenia."

Daniela B Pereira et al. Fluorescent false neurotransmitter reveals functionally silent dopamine vesicle clusters in the striatum Nature Neuroscience (2016). DOI: 10.1038/nn.4252

Top Illustration: Only 20% of synapses (red) were observed to transmit dopamine. The rest (green) were found to be silent. Credit: Sulzer Lab/Columbia University Medical Center

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