Nav: Home

Thanks, actin, for the memories

April 18, 2016

HOUSTON - (April 18, 2016) - Thank the little "muscles" in your neurons for allowing you to remember where you live, what your friends and family look like and a lot more.

New research at Rice University suggests actin filaments that control the shape of neuron cells may also be the key to the molecular machinery that forms and stores long-term memories.

The Rice lab of theoretical biological physicist Peter Wolynes reported in the Proceedings of the National Academy of Sciences a theory about how long-term memories are made; the theory is based on simulations that analyze the energy landscapes of the proteins involved.

Wolynes and his colleagues are pioneers in the development of an energy landscape theory for proteins, which enables them to build computer models of proteins to predict how they will fold. These molecular-dynamics simulations employ the principle of minimal frustration by which proteins find their most stable folded forms.

For long-term memories, stability is desirable. Wolynes and his co-authors, Rice graduate student Mingchen Chen and postdoctoral researcher Weihua Zheng, determined the path to encoding memories may lie in the way actin filaments - the "muscle" part of the cytoskeleton in every eukaryotic cell - pull upon and stabilize soluble cytoplasmic polyadenylation element binding proteins (CPEB) into longer, insoluble prion-like fibers.

Prions are proteins that, when they misfold, are thought to become self-propagating and cause infectious diseases like mad cow disease, Creutzfeldt-Jakob disease and other disorders. But their very existence and the transitions known to take place in synapses suggest properly folded prions must have a biological function, the researchers wrote. These transitions were the focus of their study.

CPEB proteins, when made in cells, first bind a few at a time in oligomers, which are coiled alpha helices. The intrinsic energy landscapes of these oligomers allow mechanical forces provided by actin to prompt a transition into longer beta strands that are much more stable. These now-stable fibers are thought to aggregate and encode memories in neurons' synaptic regions.

Wolynes said Francis Crick, co-discoverer of the structure of DNA, was onto something 20 years ago when he wrote about memory and molecular turnover. Crick puzzled over the fact that memories tend to last much longer than proteins typically do in living cells. "Crick slightly anticipates, in one sentence, that perhaps what we have is a form of protein that aggregates somewhere," he said. "By virtue of being an aggregate, it's not able to move. In that way it would be able to mark one particular synapse.

"It's obviously very difficult to study the molecular basis of memory because memory involves a fairly complex activity," Wolynes said. "You can't study it in a bacterium. You have to study it in some sort of organism that can learn.

"At the same time, it's clear that forming memories involves some very high-order neural processing and other things at the subcellular level in order to store the large amount of information you memorize. There are many steps in memory that are really not understood at all."

He said previous research shows that memories make changes in the synapse, the thousands of regions in each neuron responsible for sending electrical and chemical signals to other neurons. "Short-term memories that last less than an hour or so seem to be done through the electrical and direct biochemical circuitry. Forming these memories doesn't seem to require creating new protein," Wolynes said.

Researchers who conducted experiments with sea slugs poisoned to prevent them from synthesizing proteins seemed to confirm that, he said. "They found these snails were able to memorize things for short periods of time but not for periods of hours when protein synthesis was stopped."

Chen, who led the Rice research, knew from the literature that actin has the ability to bind oligomeric CPEB. This fact, along with the computer simulation, suggests that the mechanical force provided by actin can restructure CPEB into a longer fiber with new hydrogen bonds between the coils. Wolynes said that the restructuring not only forces CPEB to a lower-energy, prion-like state, but also allows the prion to bind an RNA sequence that otherwise prevents more actin from being synthesized. The resulting feedback loop further stabilizes the memory.

"We still don't understand the beginning of the process, how you go from short-term to long-term memory," he said. "But we can now see that actin starts to form in a particular location in response to electrical signals. The actin then takes any CPEB oligomers that are around and activates them, which makes more actin and causes the formation of a self-replicating prion of the CPEB. That prion aggregates until it stops, changing the structure of the synapse in a way that should last for a very long period of time, perhaps decades."

Wolynes said he put Chen on the job with few expectations. "I give starting students a project I think will teach them the tools we use to look at protein dynamics," he said. "It's usually a somewhat far-outish project, and if they don't get anywhere, I won't feel sad.

"So I said, 'Why don't we look at this protein that (Eric) Kandel and (Susan) Linquist said was involved in memory, this CPEB protein.'"

Wolynes said many neurobiologists have followed up on that pioneering work with sea slugs. "But we add a new element by being able to look at the structures of these proteins and to predict the thermodynamics of the process," he said. "We now can see how the force of the cytoskeleton can complete a feedback loop that allows the memories to be preserved."

Wolynes considers the new study a beachhead to launch others to determine the entire process of how memories form, as well as the implications for diseases like Alzheimer's and Parkinson's that involve protein aggregation.
-end-
The National Institute of General Medical Sciences supported the research. The researchers used the National Science Foundation (NSF)-supported DAVinCI supercomputer administered by Rice's Ken Kennedy Institute for Information Technology.

Wolynes is the D.R. Bullard-Welch Foundation Professor of Science, a professor of chemistry, of biochemistry and cell biology, of physics and astronomy and of materials science and nanoengineering at Rice and a senior investigator of the NSF-funded Center for Theoretical Biological Physics at Rice.

Read the abstract at http://www.pnas.org/cgi/doi/10.1073/pnas.1602702113

This news release can be found online at http://news.rice.edu/2016/04/18/thanks-actin-for-the-memories/

Follow Rice News and Media Relations via Twitter @RiceUNews.

Video:

https://youtu.be/F73xSp09nrI

A Rice University computer simulation shows how actin pulls upon and stabilizes soluble proteins known as CPEB into longer, insoluble prion-like fibers, a process believed to be key to stabilizing long-term memories.

Animated GIF:

http://news.rice.edu/files/2016/04/0418_MEMORY-ANIMGIF-large-191t7nv.gif

http://news.rice.edu/files/2016/04/0418_MEMORY-ANIMGIF-small-1cmqkoj.gif

Related Materials:

Wolynes Research Lab: http://wolynes.rice.edu/node/129

Center for Theoretical Biological Physics: https://ctbp.rice.edu

Rice Department of Bioengineering: http://bioe.rice.edu

Images for download:

http://news.rice.edu/files/2016/03/0304_MEMORY-1-web-1r6jeks.jpg

From left, Rice University graduate student Mingchen Chen, postdoctoral researcher Weihua Zheng and theoretical biological physicist Peter Wolynes co-authored a paper explaining a complex feedback loop between actin filaments and aggregating proteins in neurons that appears to be key to the formation of long-term memories. (Credit: Jeff Fitlow/Rice University)

http://news.rice.edu/files/2016/04/0304_MEMORY-2-web-22g7zt5.jpg

Actin pulls upon and stabilizes soluble cytoplasmic polyadenylation element binding proteins into longer, insoluble prion-like fibers, a process believed to be key to stabilizing long-term memories. Rice University researchers simulated the force (F) applied by actin through computer models that predict how proteins are likely to find their least-energetic (and most stable) states. (Credit: Mingchen Chen/Rice University)

Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation's top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,910 undergraduates and 2,809 graduate students, Rice's undergraduate student-to-faculty ratio is 6-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice is ranked No. 1 for best quality of life and for lots of race/class interaction by the Princeton Review. Rice is also rated as a best value among private universities by Kiplinger's Personal Finance. To read "What they're saying about Rice," go to http://tinyurl.com/AboutRiceUniversity.

David Ruth
713-348-6327
david@rice.edu

Mike Williams
713-348-6728
mikewilliams@rice.edu

Rice University

Related Memory Articles:

Memory boost with just one look
HRL Laboratories, LLC, researchers have published results showing that targeted transcranial electrical stimulation during slow-wave sleep can improve metamemories of specific episodes by 20% after only one viewing of the episode, compared to controls.
VR is not suited to visual memory?!
Toyohashi university of technology researcher and a research team at Tokyo Denki University have found that virtual reality (VR) may interfere with visual memory.
The genetic signature of memory
Despite their importance in memory, the human cortex and subcortex display a distinct collection of 'gene signatures.' The work recently published in eNeuro increases our understanding of how the brain creates memories and identifies potential genes for further investigation.
How long does memory last? For shape memory alloys, the longer the better
Scientists captured live action details of the phase transitions of shape memory alloys, giving them a better idea how to improve their properties for applications.
A NEAT discovery about memory
UAB researchers say over expression of NEAT1, an noncoding RNA, appears to diminish the ability of older brains to form memories.
Molecular memory can be used to increase the memory capacity of hard disks
Researchers at the University of Jyväskylä have taken part in an international British-Finnish-Chinese collaboration where the first molecule capable of remembering the direction of a magnetic above liquid nitrogen temperatures has been prepared and characterized.
Memory transferred between snails
Memories can be transferred between organisms by extracting ribonucleic acid (RNA) from a trained animal and injecting it into an untrained animal, as demonstrated in a study of sea snails published in eNeuro.
An immunological memory in the brain
Inflammatory reactions can change the brain's immune cells in the long term -- meaning that these cells have an 'immunological memory.' This memory may influence the progression of neurological disorders that occur later in life, and is therefore a previously unknown factor that could influence the severity of these diseases.
Anxiety can help your memory
Anxiety can help people to remember things, a study from the University of Waterloo has found.
Pores with a memory
Whether for separation processes, photovoltaics, catalysis, or electronics, porous polymer membranes are needed in many fields.
More Memory News and Memory Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.