What are memories made of? New study sheds light on key protein

January 26, 2018 by Lisa Marshall, University of Colorado at Boulder
Credit: CC0 Public Domain

Ask a nonscientist what memories are made of and you'll likely conjure images of childhood birthday parties or wedding days. Charles Hoeffer thinks about proteins.

For five years, the assistant professor of integrative physiology at CU Boulder has been working to better understand a called AKT, which is ubiquitous in tissue and instrumental in enabling the brain to adapt to new experiences and lay down new memories.

Until now, scientists have known very little about what it does in the brain.

But in a new paper funded by the National Institutes of Health, Hoeffer and his co-authors spell it out for the first time, showing that AKT comes in three distinct varieties residing in different kinds of and affecting in very distinct ways.

The discovery could lead to new, more targeted treatments for everything from glioblastoma—the brain cancer Sen. John McCain has—to Alzheimer's disease and schizophrenia.

"AKT is a central protein that has been implicated in a bevy of yet we know amazingly little about it," Hoeffer said. "Our paper is the first to comprehensively examine what its different forms are doing in the brain and where."

Discovered in the 1970s and known best as an "oncogene" (one that, when mutated, can promote cancer), AKT has more recently been identified as a key player in promoting "synaptic plasticity," the brain's ability to strengthen cellular connections in response to experience.

"Let's say you see a and you are scared and your brain wants to form a of what's going on. You have to make new proteins to encode that memory," he said. AKT is one of the first proteins to come online, a central switch that turns on the memory factory.

But not all AKTs are created equal.

For the study, Hoeffer's team silenced the three different isoforms, or varieties, of AKT in mice and observed their brain activity.

They made a number of key discoveries:

AKT2 is found exclusively in astroglia, the supportive, star-shaped cells in the brain and spinal cord that are often impacted in brain cancer and brain injury.

"That is a really important finding," said co-author Josien Levenga, who worked on the project as a postdoctoral researcher at CU Boulder. "If you could develop a drug that targeted only AKT2 without impacting other forms, it might be more effective in treating certain issues with fewer side-effects."

The researchers also found that AKT1 is ubiquitous in neurons and appears to be the most important in promoting the strengthening of synapses in response to experience, aka memory formation. (This finding is in line with previous research showing that mutations in AKT1 boost risk of schizophrenia and other brain disorders associated with a flaw in the way a patient perceives or remembers experiences.)

AKT3 appears to play a key role in brain growth, with mice whose AKT3 gene is silenced showing smaller brain size.

"Before this, there was an assumption that they all did basically the same thing in the same cells in the same way. Now we know better," Hoeffer said.

He notes that pan-AKT inhibitors have already been developed for cancer treatment, but he envisions a day when drugs could be developed to target more specific versions of the protein (AKT1 enhancers for Alzheimer's and schizophrenia, AKT2 inhibitors for cancer), leaving the others forms untouched, preventing side-effects.

More animal research is underway to determine what happens to behavior when different forms of the protein go awry.

"Isoform specific treatments hold great promise for the design of targeted therapies to treat neurological diseases with much greater efficacy and accuracy than those utilizing a one-size-fits-all approach," the authors conclude. "This study is an important step in that direction."

The study is published in eLife.

Explore further: Brain's immune system may be key to better treatments for psychiatric disorders

More information: eLife, DOI: 10.7554/eLife.30640.001

Related Stories

Brain's immune system may be key to better treatments for psychiatric disorders

January 4, 2018
Between the ages of two and four, the human brain has an estimated one quadrillion synapses – the electrical connections between neurons. That is the highest it will ever have, but as the world is not run by 3-year-olds, ...

Scientists develop protein with potential to modify brain function, memory in mice and fish

June 6, 2016
Scientists at USC have developed a new tool to modify brain activity and memory in targeted ways, without the help of any drugs or chemicals.

Drug restores cells and memories in Alzheimer's mouse models

July 6, 2017
A new drug can restore memories and connections between brain cells in mice with a model of Alzheimer's disease, a new Yale-led study suggests.

Neuroscientists call for more comprehensive view of how brain forms memories

July 5, 2017
Neuroscientists from the University of Chicago argue that research on how memories form in the brain should consider activity of groups of brain cells working together, not just the connections between them.

Nicotine normalizes brain activity deficits that are key to schizophrenia

January 23, 2017
A steady stream of nicotine normalizes genetically-induced impairments in brain activity associated with schizophrenia, according to new research involving the University of Colorado Boulder. The finding sheds light on what ...

Origin of synaptic pruning process linked to learning, autism and schizophrenia identified

May 2, 2016
Research led by SUNY Downstate Medical Center has identified a brain receptor that appears to initiate adolescent synaptic pruning, a process believed necessary for learning, but one that appears to go awry in both autism ...

Recommended for you

Protein droplets keep neurons at the ready and immune system in balance

August 15, 2018
Inside cells, where DNA is packed tightly in the nucleus and rigid proteins keep intricate transport systems on track, some molecules have a simpler way of establishing order. They can self-organize, find one another in crowded ...

Self-control develops gradually in adolescent brain

August 15, 2018
Different parts of the brain mature at different times, which may help to explain impulsive behaviors in adolescence, suggest researchers from Penn State and the University of Pittsburgh.

Research reveals that what we see is not always what we get

August 15, 2018
Researchers are helping to explain why some people anticipate and react to fast-moving objects much quicker than others.

New approach to treating chronic itch

August 15, 2018
Researchers at the University of Zurich have discovered a new approach to suppressing itch by targeting two receptors in the spinal cord with the right experimental drug. In a series of experiments in mice and dogs, they ...

Immune cells in the brain have surprising influence on sexual behavior

August 14, 2018
Researchers have found a surprising new explanation of how young brains are shaped for sexual behavior later in life.

Scientists pinpoint brain networks responsible for naming objects

August 14, 2018
Scientists at The University of Texas Health Science Center at Houston (UTHealth) have identified the brain networks that allow you to think of an object name and then verbalize that thought. The study appeared in the July ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Parsec
not rated yet Jan 27, 2018
I wonder if AKT1 enhancers would assist normal memory? I can see a science fiction plt glimmers on the horizon...

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.