Engineered cells reveal changes associated with learning, memory and reward
Scientists have created cells with fluorescent dyes that change color in response to specific neurochemicals. By implanting these cells into living mammalian brains, they have shown how neurochemical signaling changes as a food reward drives learning, they report in Nature Methods online October 26.
These cells, called CNiFERs (pronounced "sniffers"), can detect small amounts of a neurotransmitter, either dopamine or norepinephrine, with fine resolution in both location and timing. Dopamine has long been of interest to neuroscientists for its role in learning, reward, and addiction.
"Dopamine is a ubiquitous molecule in the brain that signals 'mission accomplished.' It serves as the key indicator during almost all aspects of learning and the formation of new memories," said David Kleinfeld professor of physics at UC San Diego, who directed the work. "Disruptions to dopamine signaling lie at the heart of schizophrenia and addiction." Kleinfeld also holds appointments in neurobiology, and electrical and computer engineering.
Neuroscientists have long sought to measure dopamine in the brain during controlled conditions. But the chemistry of dopamine is so close to that of norepinephrine that fast and accurate measurements of dopamine, not confounded by other molecules, have eluded scientists.
Kleinfeld and Paul Slesinger, a professor of neuroscience at Icahn School of Medicine at Mount Sinai, New York, developed CNiFERs to meet this challenge. These modified cells can be inserted into the brains of animals to observe changes in neural signalling in real time.
Arnaud Muller and Victory Joseph, working Kleinfeld's laboratory, implanted CNiFERs into the frontal cortex in mice, then watched how signaling changed as the mice learned to associate a sound with a sweet reward.
This is classical conditioning, in which a tone that reliably preceded a drop of sweet water came to elicit anticipatory licking over time. The researchers found that release of dopamine, but not norepinephrine, tracked this change. That is, dopamine was initially released with the reward, but began to be released earlier, with the tone, as the mice learned to associate this previously neutral signal with something pleasant. In mice that failed to learn or made only a weak association, the anticipatory release of dopamine was reduced as well.
Brain researchers have long suspected this link. But because the design of these cellular reporters is quite versatile, a number of different chemical signals of interest could be tracked using the same approach.
"This work provides a path for the design of cells that report a large and diverse group of signaling molecules in the brain," Kleinfeld said.
The National Institute on Drug Abuse, National Institute of Biomedical Imaging and Bioengineering and Hoffman-La Roche provided funding for this work.
Susan Brown | Eurek Alert!
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Earth Sciences
24.03.2017 | Health and Medicine
24.03.2017 | Earth Sciences