Scientists at Emory University School of Medicine have uncovered how a structural component inside neurons performs two coordinated dance moves when the connections between neurons are strengthened.
The results are published online in the journal Nature Neuroscience, and will appear in a future print issue.
In experiments with neurons in culture, the researchers can distinguish two separate steps during long-term potentiation, an enhancement of communication between neurons thought to lie behind learning and memory. Both steps involve the remodeling of the internal "skeletons" of dendritic spines, small protrusions on the surface of a neuron that receive electrical signals from neighboring cells.
The results hint at why people with Williams syndrome, a developmental disorder caused by a deletion of several genes, including one that alters dendritic spine remodeling, have such an unusual blend of cognitive strengths and weaknesses.
The senior author of the paper is James Zheng, PhD, professor of cell biology and neurology at Emory University School of Medicine. The paper's co-first authors are graduate student Jiaping Gu, now a postdoctoral researcher at New York University, postdoc Chi Wai Lee and graduate student Yanjie Fan.
"We've been looking at the remodeling of dendritic spines, which is a fundamental process for reshaping circuits in the brain," Zheng says. "The anatomy of dendritic spines is altered in many diseases, such as fragile X syndrome and schizophrenia, as well as neurodegenerative disorders like Alzheimer's."
During the process of long-term potentiation, dendritic spines both enlarge and display a greater density of neurotransmitter receptors, the receiver dishes that allow neurons to detect the waves of chemicals other neurons are sending them.
Zheng's team studied this process by engineering a type of neurotransmitter receptor to be fluorescent when introduced into neurons. This particular engineered receptor is fluorescent only when it's on the surface of a cell.
"This allows us to directly visualize the addition of these receptors to the spine surface from their internal stores," he says.
The researchers tested how the movement of the receptors was tied to remodeling of the internal skeleton of the cell, by using drugs that either loosen or freeze the actin cytoskeleton, which forms the main structural support inside dendritic spines.
They then investigated the family of proteins called ADF (actin depolymerizing factor)/cofilin, which Zheng describes as acting like a pair of scissors, severing the links of the actin cytoskeleton.
"Our results suggest that there are two activities that need to be coordinated to strengthen dendritic spines: the cell has to cut actin filaments in order to allow receptors in storage to be added to the surface, but then it has to put away the scissors and stabilize and enlarge the spines," Zheng says.
Williams syndrome is a rare developmental disorder caused by a chromosomal deletion spanning 28 genes, several of which may contribute to changes in cognitive development. One of the genes thought to be responsible encodes the enzyme LIM kinase 1. LIM kinase deactivates ADF/cofilin, which means neurons in Williams syndrome may have an altered ability to remodel dendritic spines.
Williams syndrome impairs affected individuals' perceptions of space as well as their ability to make social judgments, but tends to leave other functions relatively intact. Individuals with Williams syndrome are noted to have an affinity for language and music.
"Cytoskeletal remodeling is required for some aspects of long-term potentiation but also needs to be reigned in. If we change LIM kinase or ADF/cofilin and shift the balance of the cytoskeletal remodeling, that could affect some cognitive processes and not others," Zheng proposes. He also believes that the actin cytoskeleton and its regulation by ADF/cofilin, can be a likely target affected by many neurological disorders involving impaired brain functions.
Pharmaceutical companies have been testing inhibitors of LIM kinases as potential drugs for treating glaucoma, cancer and other diseases. Zheng's team's results indicate that manipulating LIM kinase with drugs could end up perturbing or impairing cognitive processes, he says.
"However, it also could mean that there is a window of time where you could possibly enhance learning or memory formation, based on the dynamics of dendritic spine remodeling," he says.
The research was supported by the National Institutes of Health.
Gu et al. ADF/cofilin-mediated actin dynamics regulate AMPA receptor trafficking during synaptic plasticity. Nature Neurosci. Advance online pub. (2010)
Quinn Eastman | EurekAlert!
What the world's tiniest 'monster truck' reveals
23.08.2017 | American Chemical Society
Treating arthritis with algae
23.08.2017 | Empa - Eidgenössische Materialprüfungs- und Forschungsanstalt
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy