Study finds only a small portion of synapses may be active during neurotransmission



New optical technique, used in mice, offers detailed face at how dopamine works in the brain

NEW YORK, NY (Feb. 25, 2016) — Columbia University scientists be under the necessity developed a new optical technique to study in what state information is transmitted in the intellectual faculties of mice. Using this method, they set up that only a small portion of synapses — the connections between cells that control brain activity–may subsist active at any given time. 

The study was published in the latest termination of Nature Neuroscience.

“Understanding how we finish complex tasks, such as learning and remembrance, requires us to look at in what state our brains transmit key signals — called neurotransmitters — across synapses from one neuron to one more,” said David Sulzer, PhD, professor of neurobiology in Psychiatry, Neurology, and Pharmacology at Columbia University Medical Center (CUMC). “Older techniques excepting that revealed what was going on in full groups of synapses. We needed a wont to observe the neurotransmitter activity of individual synapses, to assistance us better understand their intricate behavior.”

To obtain a detailed view of synaptic mode of action, Sulzer’s team collaborated with the laboratory of Dalibor Sames, PhD, couple professor of chemistry at Columbia, to lay open a novel compound called fluorescent wrong neurotransmitter 200 (FFN200). When added to brain web or nerve cells from mice, FFN200 mimics the brain‘s unaffected neurotransmitters and allows researchers to behold on chemical messaging in action.

Using a fluorescence microscope, the researchers were expert to view the release and reuptake of dopamine — a neurotransmitter involved in motor learning, habit formation, and reward-seeking manner — in individual synapses. When all the neurons were electrically stimulated in a model of brain tissue, the researchers expected every one of the synapses to release dopamine. Instead, they establish that less than 20 percent of dopaminergic synapses were brisk following a pulse of electricity.

“Why are in that place these large reservoirs of synapses that are inactive?” said Dr. Sames, a co-former of the paper. “Perhaps these noiseless terminals hint at a mechanism of notice coding in the brain that’s to this time to be revealed.”

The study’s authors figure to pursue this hypothesis in coming events experiments, as well as examine in what plight other neurotransmitters behave.

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


The study is titled, “Fluorescent treacherous neurotransmitter reveals functionally silent dopamine cyst clusters in the striatum.” The other contributors are: Daniela B. Pereira, Yvonne Schmitz, Josef Meszaros, Paolomi Merchant, Gang Hu, Shu Li, Adam Henke, Jose E. Lizardi-Ortiz, Richard J. Karpowicz, Jr., Travis J. Morgenstern, Mark S. Sonders, Ellen Kanter, Pamela C. Rodriguez, and Eugene V. Mosharov,. The study was supported ~ dint of. grants from the G. Harold & Leila Y. Mathers Charitable Foundation, the National Institute of Mental Health (grants R01MH086545 and R01MH108186), the National Institute of Neurological Disorders and Stroke (largess R01NS075222), the National Science Foundation, the JPB, McKnight and Michael J. Fox Foundation, and the Udall Center of Excellence as far as concerns Parkinson’s Disease Research.

The Parkinson’s Disease Foundation also supported this work.

The authors declare competing monetary interests: details are available in the online lection of the paper. D. Sulzer and D. Sames were listed as inventors on a patent (8,337,941) capsule FFN200 and a patent application (13/575,535) case FFN102, com- pounds employed in this study.

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