05:46pm Tuesday 12 December 2017

Progress Made on Columbia University Technology for High-Resolution Optical Imaging of Synaptic Activity in the Brain

NEW YORK Columbia University researchers have developed a novel fluorescent probe for optical imaging and measurement of synaptic activity in the brain.

Born of the need for a tool that would permit direct visualization of neurotransmitter release and uptake, and measurement of synaptic activity, the laboratories of Dalibor Sames, PhD, an associate professor in Columbia’s Department of Chemistry, and David Sulzer, PhD, a professor of neurobiology at Columbia University Medical Center, collaborated to create several Fluorescent False Neurotransmitters (FFNs), a class of highly efficient optical imaging probes that light up sufficiently enough to provide resolution at the individual synaptic level but at concentrations that do not interfere with normal synaptic function.

It’s well-known that memory, decision making and learning require activation and modification of synapses in the brain. This synaptic transmission involves the accumulation of neurotransmitters in vesicles within the cytoplasm of the pre-synaptic neuron; neurotransmitters are then released when the vesicle fuses with the plasma membrane of the cell.

synapse
Neuron preparing to transmit a signal across the synapse. Illustration: Graham Johnson Medical Media.

Previous ways of imaging neurotransmitters have allowed researchers to measure post-synaptic neuronal activity and to observe the vesicle-membrane fusion process but, until now, it has not been possible to observe actual neurotransmitter release from individual synapses.

Columbia, together with Ascent Scientific, have now entered into a license agreement for an FFN designated 511, which promises to help scientists illuminate the mechanisms that may underlie mental illnesses and neuropathologies.

In a recent Science publication, Dr. Sames and his colleagues described a new form of synaptic plasticity, revealed by FFN511, where individual dopaminergic synapses respond differently to stimulus frequency (which emulates brain activity). FFN511 enabled the team to acquire optical measurements of presynaptic changes, at a spatial resolution up to one micromolar, that were simply not possible to achieve with existing probes or electrophysiological methods.

“We believe that FFN511 has the potential to become an essential research tool for neuroscientists studying the synaptic transmission of dopamine as well as for drug discovery efforts seeking to identify improved blockers and enhancers of dopamine transporter activity,” Dr. Sulzer said.

Blocking of dopamine active transport proteins has been shown to ameliorate symptoms in pre-clinical models of Parkinson’s Disease, and drugs that target dopamine transporters and receptors are used to treat ADHD, bipolar disorder and schizophrenia.

Sulzer

Dr. David Sulzer at work in his lab.

“This groundbreaking tool provides a means for scientists to optically measure important presynaptic processes at the synaptic terminal level of discrete neurons,” said Steve Roome, Commercial Director for Ascent Scientific. “We are delighted to be the first commercial supplier to bring FFN511 to the life sciences community.”

“Broadly, FFNs provide a means of characterizing neurotransmitter release at the level of individual synapses, even on the same neuron. This capability is very important for understanding how the nervous system activates specific pathways and actions, and how it is altered by learning and development,” explains Beth Kauderer of Columbia Technology Ventures, the technology licensing office of Columbia University. “We expect that FFNs will be useful for both fundamental and applied neurobiology research, across a wide range of areas including learning, neurodegeneration and drug addiction,” Kauderer says.

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A leading academic and research university, Columbia University continually seeks to advance the frontiers of knowledge and to foster a campus community deeply engaged in understanding and addressing the complex global issues of our time. Columbia University’s technology transfer office, Columbia Technology Ventures, manages Columbia’s intellectual property portfolio and serves as the university’s gateway for companies and entrepreneurs seeking novel technology solutions.  Columbia Technology Venture’s core mission is to facilitate the transfer of inventions from academic research to outside organizations for the benefit of society on a local, national and global basis.  For more information on Columbia Technology Ventures, please visit www.techventures.columbia.edu.

Columbia University Medical Center
provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians & Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the largest medical research enterprise in New York City and state and one of the largest in the United States. For more information, please visit www.cumc.columbia.edu.


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