New research by scientists at the University of Massachusetts Medical School shows at the single cell level how an external stimulus sets off a molecular chain reaction in the transparent roundworm C. elegans, a process in which a single neurotransmitter coordinates and times two separate actions.
These findings shed new light on how neurons translate sensory input into actions and may one day pave the way to understanding how misfiring neurons contribute to motor symptoms in neurological diseases such as Parkinson's disease. Details of the study were published online by PLOS Biology.
"We've known the broad outline of how a behavior circuit works-a stimulus starts a neuronal cascade, which ultimately activates a muscle cell-for decades," said Mark Alkema, PhD, assistant professor of neurobiology. "The details about how this process works, however, such as which neurotransmitters act through which receptors in which neurons have remained a mystery for even the simplest of behaviors.
"This research provides an answer to the simple question of how the worm turns around and the broader question of how a behavioral sequence is produced on a sub-cellular level. In time, understanding voluntary movement in humans will require answering the same questions about the timing and location of neurons and neurotransmitters-only in the infinitely more complex variety of circuits in the human nervous system," said Dr. Alkema.
Roundworms move by alternately relaxing and contracting ventral and dorsal muscles along both sides of its body. As the animal moves forward, it uses its head to probe for possible threats. A gentle touch to the head of the worm initiates an escape response resulting in the animal ceasing head movements and quickly moving backwards. This initial reaction is closely followed by a deep ventral turn allowing it to move away in the opposite direction.
Earlier studies have shown that tyramine, a monoamine neurotransmitter akin to noradrenaline in humans, is involved in the C. elegans escape response. Specifically, C. elegans have a pair of tyraminergic motor neurons that are essential for coordinating the initial suppression of head movement and the backing response. These neurons release tyramine, which works through a fast-acting ion channel called LGC-55 to inhibit forward movement and relax the neck muscles. How the animal coordinates this movement with the subsequent deep turn that allows it to complete the change in direction and move away from the threat, however, was unknown. In this study, the authors provide evidence that links this initial phase of the escape response to the later stages in which the worm makes a sharp turn and navigates away from the danger.
When C. elegans are placed on a surface containing a high concentration of tyramine they become immobilized. Alkema and colleagues found that this paralysis could be overcome by mutating the C. elegans gene responsible for encoding the G-protein coupled receptor SER-2. Additionally, they found that the SER-2 receptor was active in a set of 13 neurons residing along the ventral nerve cord. The synapses of these neurons were connected to corresponding ventral muscles cells along one side of the worm's body.
Further experiments revealed that the same monoamine neurotransmitter-tyramine-responsible for the initial phase of the escape response was also responsible for activating the slow-acting G-protein coupled receptor SER-2. Activation of this receptor inhibited release of the neurotransmitter GABA and facilitated contraction of the ventral muscles, allowing the animal to complete its turn and resume movement in the opposite direction.
"This study shows how tyramine works through separate receptors to produce a complex behavior requiring the temporal coordination of independent motor programs," said Alkema. "Acting through the fast-acting ionotropic receptor LGC-55, the animal completes the initial movement by ceasing head movement and backing away. At the same time, the slow-acting SER-2 receptor is also being activated by tyramine to complete the turn and facilitate movement in the opposite direction.
"It is the different receptors that allow for the coordination of these actions by the same neurotransmitter," said Alkema. "This indicates that tyramine, much like adrenergic signaling in mammals, coordinates different aspects of the flight response. It's possible that temporally coordinated activation of ionotropic and metabotropic receptors may be a common signaling motif employed across organisms to orchestrate behavioral responses and is something we will be pursing further."About the University of Massachusetts Medical School
Jim Fessenden | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
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 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy