Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The ever-changing brain: Shining a light on synaptic plasticity

20.11.2019

Researchers study key neural receptor involved in learning and memory

Synapses - specialized structures in neurons - allow these nerve cells to communicate with one another. In the synapse, one neuron emits chemical messengers called neurotransmitters, and an apposed neuron receives them using tiny structures called receptors.


In the membrane outside the synapse, the AMPA receptor subunit concentrations are low; subunits mainly exist as individuals or form pairs. Within the synapse, the AMPA receptor subunit concentrations are high, and tetramers form. Tetramers lifetimes are about 0.2 seconds.

Credit: OIST

A specific type of receptor, the AMPA receptor, plays a crucial role in learning and memory processes. However, scientists don't yet fully understand how these AMPA receptors form and work.

Now, researchers in the Membrane Cooperativity Unit at the Okinawa Institute of Science and Technology Graduate University (OIST) in Japan, in collaboration with researchers from universities across Japan, have found that AMPA receptors form and disintegrate continually, within a fraction of a second, rather than existing as stable entities.

The scientists' findings, published in Nature Communications, may help clarify early stages of synaptic plasticity: neural activity that is key for learning and memory. The research may also have pharmacological applications in the treatment of epilepsy.

The changing brain

AMPA receptors are composed of four molecules, or subunits - called GluA1, 2, 3, and 4 - which unite to form structures called tetramers. Different combinations of the subunits form the tetramers; this means there are 256 possible configurations of AMPA receptor.

Scientists have long believed that these tetramers originate in the endoplasmic reticulum, the cell's "manufacturing center," before migrating to the synapses, all while retaining stable structures for hours or even days.

"This tetramer stability could actually be problematic for neurons," said Professor Akihiro Kusumi, a co-author of the study. "The synapses need AMPA receptor tetramers with different combinations of subunits as the brain learns and its neuronal circuits change. Thus, we had a gut feeling that something was terribly wrong with the accepted notion of how AMPA receptors form, migrate, and work."

Looking at AMPA receptors in motion at single-molecule resolutions

Following this intuition, the researchers put fluorescent tags on each individual subunit molecule of the AMPA receptors. Then, they tracked the molecules' movements in live cells at nanometer-precisions. They used a single-molecule fluorescence microscope and software to analyze the motion of the single molecules, a method Kusumi and his colleagues pioneered.

By studying how the AMPA receptor molecules jostled around in the membrane and bound to each other, the researchers found that the AMPA receptor subunits existed as single molecules as well as assemblies two, three, and four molecules.

Tetramers were found, but they fell apart in about 0.1 to 0.2 seconds. Then, however, the separated molecules found other partner molecules to form new assemblies of two, three, and four molecules again, continually repeating this process.

In addition, the researchers found that when the molecules formed tetramers, albeit briefly, they worked as tiny channels that opened for less than 0.1 seconds.

Since the functional tetramers are continually broken up to form new tetramers, AMPA receptor tetramers with different subunit compositions can readily be formed. This represents a novel mechanism for synaptic plasticity.

Kusumi noted that the team's findings may have medical applications. Individuals with epilepsy have an excess of glutamate, the neurotransmitter that binds to AMPA receptors in the brain. These individuals are often treated with anticonvulsants that stop glutamate from binding to AMPA receptor tetramers, but these treatments can be too overpowering, and therefore ineffective.

Kusumi believes the development of drugs that slow down the formation of tetramers with certain subunit compositions in the brain could mitigate problematic types of synaptic plasticity, thus diminishing the symptoms of epilepsy.

Media Contact

Tomomi Okubo
tomomi.okubo@oist.jp
81-989-823-447

 @oistedu

http://www.oist.jp/ 

Tomomi Okubo | EurekAlert!

More articles from Health and Medicine:

nachricht How extreme environmental conditions affect the human brain
05.12.2019 | Max-Planck-Institut für Bildungsforschung

nachricht New remote-controlled 'smart' platform helps in cardiovascular disease treatment
05.12.2019 | Chinese Academy of Sciences Headquarters

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The coldest reaction

With ultracold chemistry, researchers get a first look at exactly what happens during a chemical reaction

The coldest chemical reaction in the known universe took place in what appears to be a chaotic mess of lasers. The appearance deceives: Deep within that...

Im Focus: How do scars form? Fascia function as a repository of mobile scar tissue

Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, the team of Dr. Yuval Rinkevich, Group Leader for Regenerative Biology at the Institute of Lung Biology and Disease at Helmholtz Zentrum München, aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene - a lineage not only present in skin, but also in fascia - the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.

Fibroblasts kit - ready to heal wounds

Im Focus: McMaster researcher warns plastic pollution in Great Lakes growing concern to ecosystem

Research from a leading international expert on the health of the Great Lakes suggests that the growing intensity and scale of pollution from plastics poses serious risks to human health and will continue to have profound consequences on the ecosystem.

In an article published this month in the Journal of Waste Resources and Recycling, Gail Krantzberg, a professor in the Booth School of Engineering Practice...

Im Focus: Machine learning microscope adapts lighting to improve diagnosis

Prototype microscope teaches itself the best illumination settings for diagnosing malaria

Engineers at Duke University have developed a microscope that adapts its lighting angles, colors and patterns while teaching itself the optimal...

Im Focus: Small particles, big effects: How graphene nanoparticles improve the resolution of microscopes

Conventional light microscopes cannot distinguish structures when they are separated by a distance smaller than, roughly, the wavelength of light. Superresolution microscopy, developed since the 1980s, lifts this limitation, using fluorescent moieties. Scientists at the Max Planck Institute for Polymer Research have now discovered that graphene nano-molecules can be used to improve this microscopy technique. These graphene nano-molecules offer a number of substantial advantages over the materials previously used, making superresolution microscopy even more versatile.

Microscopy is an important investigation method, in physics, biology, medicine, and many other sciences. However, it has one disadvantage: its resolution is...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The Future of Work

03.12.2019 | Event News

First International Conference on Agrophotovoltaics in August 2020

15.11.2019 | Event News

Laser Symposium on Electromobility in Aachen: trends for the mobility revolution

15.11.2019 | Event News

 
Latest News

Swiss space telescope CHEOPS: Rocket launch set for 17 December 2019

05.12.2019 | Physics and Astronomy

Detailed insight into stressed cells

05.12.2019 | Life Sciences

State of 'hibernation' keeps haematopoietic stem cells young - Niches in the bone marrow protect from ageing

05.12.2019 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>