Overview: New sensors made from modified carbon nanotubes can visualize the release of dopamine from neurons with unprecedented resolution.
Source: TO RUB
Dopamine is an important signaling molecule for nerve cells. Until now, its concentration could not be accurately determined with both high spatial and temporal resolution. A new method has now made this possible.
A research team from Bochum, Göttingen and Duisburg used modified carbon nanotubes that glow more brightly in the presence of the messenger substance dopamine. These sensors visualize the release of dopamine from nerve cells with unprecedented resolution.
The researchers led by Professor Sebastian Kruss from the Department of Physical Chemistry at Ruhr-Universität Bochum (RUB) and Dr. James Daniel as well as professor Nils Brose of the Max Planck Institute for Multidisciplinary Sciences in Göttingen report on this in the journal PNAS from 25 May 2022.
Fluorescence changes in the presence of dopamine
The neurotransmitter dopamine controls, among other things, the reward center of the brain. If this signal transmission stops functioning, it can lead to conditions such as Parkinson’s disease. In addition, the chemical signals are altered by drugs such as cocaine and play a role in substance abuse disorders.
“Until now, however, there has been no method that could simultaneously visualize the dopamine signals with high spatial and temporal resolution,” explains Sebastian Kruss, head of the Functional Interfaces and Biosystems Group at RUB and member of the Ruhr Explores Solvation Cluster of Excellence ( RESOLV) and the International Graduate School of Neuroscience (IGSN).
This is where the new sensors come into play. They are based on ultra-thin carbon tubes, about 10,000 times thinner than a human hair. When irradiated with visible light, they glow in the near infrared range with wavelengths of 1000 nanometers and more.
“This range of light is not visible to the human eye, but it can penetrate deeper into tissue to provide better and sharper images than visible light,” says Kruss. In addition, in this range there are far fewer background signals that can distort the result.
“We systematically modified this property by binding several short nucleic acid sequences to the carbon nanotubes in such a way that they change their fluorescence when they come into contact with defined molecules,” explains Sebastian Kruss.
For example, his research group has succeeded in converting carbon nanotubes into minuscule nanosensors that bind specifically to dopamine and fluoresce more or less strongly depending on the dopamine concentration.
“We immediately realized that such sensors would be interesting for neurobiology,” says Kruss.
Coating healthy nerve cells with a sensor layer
To do this, the sensors must be placed near functioning neuronal networks. dr. Sofia Elizarova and James Daniel of the Max Planck Institute for Multidisciplinary Sciences in Göttingen have developed cell culture conditions for this, in which the nerve cells remain healthy and can be covered with an extremely thin layer of sensors.
This allowed the researchers, for the first time, to visualize individual dopamine release events along neuronal structures and gain insight into the mechanisms of dopamine release.
Kruss, Elizarova and Daniel are convinced that the new sensors have enormous potential: “They offer new insights into the plasticity and regulation of dopamine signals,” says Sofia Eizarova.
“In the long run, they could also facilitate advances in the treatment of diseases such as Parkinson’s.” In addition, even more sensors are currently being developed with which other signaling molecules can be made visible, for example to identify pathogens.
The study was conducted by researchers from the Physical Chemistry II at the Ruhr-Universität Bochum and the Max Planck Institute for Multidisciplinary Sciences in Göttingen, teams from the Institute for Physical Chemistry at the University of Göttingen, the Center for Integrative Physiology and Molecular Medicine at the University of Saarland and the Fraunhofer Institute for Microelectronic Circuits and Systems in Duisburg.
About this neurotech and dopamine research news
Original research: Closed access.
†A fluorescent nanosensor paint reveals the heterogeneity of dopamine release by neurons at individual release sitesby Sebastian Kruss et al. PNAS
A fluorescent nanosensor paint reveals the heterogeneity of dopamine release by neurons at individual release sites
The neurotransmitter dopamine (DA) regulates multiple behaviors and is disrupted in several major brain diseases. DA is released from large populations of specialized structures called axon varicosities. Determining the DA release mechanisms in such varicosities is essential for a detailed understanding of DA biology and pathobiology, but is limited by the low spatial resolution of DA detection methods.
We used a near-infrared fluorescent DA nanosensor paint, adsorbed nanosensors detecting the release of dopamine (AndromeDA), to detect DA secretion from cultured mouse dopaminergic neurons with high spatial and temporal resolution.
We found that AndromeDA detects discrete DA release events and extracellular DA diffusion and noted that DA release varies between varicosities. To systematically detect DA release hotspots, we developed a machine learning-based analysis tool.
AndromeDA allowed the simultaneous visualization of DA release for up to 100 dopaminergic varicosities, demonstrating that DA release hotspots are heterogeneous and occur in only ∼17% of all varicosities, indicating that many varicosities are functionally silent.
Using AndromeDA, we determined that DA release requires Munc13-type vesicle priming proteins, validating the utility of AndromeDA as a tool to study the molecular and cellular mechanism of DA secretion.
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