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 Study shows novel protein plays role in bacterial vaginosis
13.12.2019 | University of Arizona Health Sciences

nachricht Illinois team develops first of a kind in-vitro 3D neural tissue model
12.12.2019 | University of Illinois College of Engineering

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: Virus multiplication in 3D

Vaccinia viruses serve as a vaccine against human smallpox and as the basis of new cancer therapies. Two studies now provide fascinating insights into their unusual propagation strategy at the atomic level.

For viruses to multiply, they usually need the support of the cells they infect. In many cases, only in their host’s nucleus can they find the machines,...

Im Focus: Cheers! Maxwell's electromagnetism extended to smaller scales

More than one hundred and fifty years have passed since the publication of James Clerk Maxwell's "A Dynamical Theory of the Electromagnetic Field" (1865). What would our lives be without this publication?

It is difficult to imagine, as this treatise revolutionized our fundamental understanding of electric fields, magnetic fields, and light. The twenty original...

Im Focus: Highly charged ion paves the way towards new physics

In a joint experimental and theoretical work performed at the Heidelberg Max Planck Institute for Nuclear Physics, an international team of physicists detected for the first time an orbital crossing in the highly charged ion Pr⁹⁺. Optical spectra were recorded employing an electron beam ion trap and analysed with the aid of atomic structure calculations. A proposed nHz-wide transition has been identified and its energy was determined with high precision. Theory predicts a very high sensitivity to new physics and extremely low susceptibility to external perturbations for this “clock line” making it a unique candidate for proposed precision studies.

Laser spectroscopy of neutral atoms and singly charged ions has reached astonishing precision by merit of a chain of technological advances during the past...

Im Focus: Ultrafast stimulated emission microscopy of single nanocrystals in Science

The ability to investigate the dynamics of single particle at the nano-scale and femtosecond level remained an unfathomed dream for years. It was not until the dawn of the 21st century that nanotechnology and femtoscience gradually merged together and the first ultrafast microscopy of individual quantum dots (QDs) and molecules was accomplished.

Ultrafast microscopy studies entirely rely on detecting nanoparticles or single molecules with luminescence techniques, which require efficient emitters to...

Im Focus: How to induce magnetism in graphene

Graphene, a two-dimensional structure made of carbon, is a material with excellent mechanical, electronic and optical properties. However, it did not seem suitable for magnetic applications. Together with international partners, Empa researchers have now succeeded in synthesizing a unique nanographene predicted in the 1970s, which conclusively demonstrates that carbon in very specific forms has magnetic properties that could permit future spintronic applications. The results have just been published in the renowned journal Nature Nanotechnology.

Depending on the shape and orientation of their edges, graphene nanostructures (also known as nanographenes) can have very different properties – for example,...

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

Supporting structures of wind turbines contribute to wind farm blockage effect

13.12.2019 | Physics and Astronomy

Chinese team makes nanoscopy breakthrough

13.12.2019 | Physics and Astronomy

Tiny quantum sensors watch materials transform under pressure

13.12.2019 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>