Navigation Links
Scientists glimpse dance of skeletons inside neurons

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.


Contact: Holly Korschun
Emory University

Related biology news :

1. Jefferson scientists deliver toxic genes to effectively kill pancreatic cancer cells
2. Scientists identify novel inhibitor of human microRNA
3. Argonne scientists peer into heart of compound that may detect chemical, biological weapons
4. MU scientists go green with gold, distribute environmentally friendly nanoparticles
5. Scientists identify gene that may contribute to improved rice yield
6. Scientists discover why a mothers high-fat diet contributes to obesity in her children
7. MU scientists see how HIV matures into an infection
8. Earth scientists keep an eye on Texas
9. Thinking it through: Scientists call for policy to guide biofuels industry toward sustainability
10. Scientists identify a molecule that coordinates the movement of cells
11. Scientists Find new migratory patterns for Mediterranean and Western Atlantic bluefin tuna
Post Your Comments:
(Date:10/29/2015)... Mich. , Oct. 29, 2015  Rubicon ... Genomics for U.S. distribution of its DNA library ... kit and Rubicon,s new ThruPLEX Plasma-seq kit. ThruPLEX ... enable the preparation of NGS libraries for liquid ... for diagnostic and prognostic applications in cancer and ...
(Date:10/29/2015)... 2015 NXTD ) ("NXT-ID" ... on the growing mobile commerce market and creator ... a leading marketplace to discover and buy innovative ... wallet on StackSocial for this holiday season.   ... "Company"), a biometric authentication company focused on the ...
(Date:10/27/2015)... NEW YORK , Oct. 27, 2015 ... the major issues of concern for various industry verticals ... This is due to the growing demand for secure ... practices in various ,sectors, such as hacking of bank ... concerns for electronic equipment such as PC,s, laptops, and ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... Therapeutics, Inc. (NASDAQ: HALO ) will be presenting at the ... on Wednesday, December 2 at 9:30 a.m. ET/6:30 a.m. PT . ... a corporate overview. th Annual Oppenheimer Healthcare Conference ... a.m. PT . Jim Mazzola , vice president of ... --> th Annual Oppenheimer Healthcare Conference in ...
(Date:11/24/2015)... 2015  Clintrax Global, Inc., a worldwide provider of clinical research ... announced that the company has set a new quarterly earnings record ... quarter growth posted for Q3 of 2014 to Q3 of 2015. ... Mexico , with the establishment of an Asia-Pacific ... United Kingdom and Mexico ...
(Date:11/24/2015)... New York , November 24, 2015 ... to a recent market research report released by Transparency ... projected to expand at a CAGR of 17.5% during ... "Non-invasive Prenatal Testing Market - Global Industry Analysis, Size, ... estimates the global non-invasive prenatal testing market to reach ...
(Date:11/24/2015)... ... November 24, 2015 , ... InSphero AG, the leading ... culture models, has promoted Melanie Aregger to serve as Chief Operating Officer. ... on the management team and was promoted to Head of InSphero Diagnostics ...
Breaking Biology Technology: