US scientists studying brain cells in mice found that a single cell in the front part of the brain can hold fleeting traces of memories on its own for as long as a minute and perhaps even longer: it behaves a bit like RAM, the short term memory storage used by computers.
The research appears as a paper in the 25 January online issue of the journal Nature Neuroscience and is the work of senior author Dr Don Cooper, assistant professor of psychiatry at The University of Texas (UT) Southwestern Medical Center at Dallas, and colleagues.
This is the first study to find the exact signal that enables a brain cell to hold information temporarily. The discovery could help us better understand and treat addiction, attention disorders, and memory loss due to things like stress and trauma, said Cooper.
Scientists already know that permanent memories get stored when glutamate (an amino acid) switches on ion channels of brain cells to reorganize and strengthen the way they connect to each other. But this takes time, several minutes to several hours, to fire up and then turn off, and reacts too slowly to be useful as a temporary store or buffer of information that comes in much faster.
Cooper and colleagues found that “inputs” of small chunks of information that last less than a second trigger a single-cell effect in the most highly evolved part of the brain, an effect that is called “metabotropic glutamate transmission” that acts like a temporary buffer to hold moment to moment information.
“It’s more like RAM [random access memory] on a computer than memory stored on a disk,” explained Cooper.
“The memory on the disk is more permanent and you can go back and access the same information repeatedly. RAM memory is rewritable temporary storage that allows multitasking,” he added.
The study’s findings enhance our knowledge about how the brain stores information that changes rapidly; Cooper compares it to the temporary memory a card shark uses when counting cards during a game of Black Jack. It can also be disrupted quite easily with alcohol and noise, as many casinos have discovered, he said.
Using nanoscale electrodes, Cooper and colleagues found that when a particular receptor in the brain cells of mice is switched on, it triggers a cascade of signals that use calcium to hold a memory trace. The particular receptor is called mGluR5 (metabotropic glutamate receptor 5), and the process occurs inside individual cells, unlike long term memory which involves proteins re-arranging connections between cells.
Cooper and colleagues did a further experiment to see how their discovery might affect conditions like addiction, where the neurochemical dopamine plays an important role. Just the right amount of dopamine helps people be focused and decisive.
Cooper and colleagues found that activating a particular type of dopamine receptor helped the brain cells to “focus” and made the memory trace less susceptible to distraction.
They also found that repeated exposure to addictive levels of cocaine in animals bred to study drug addiciton, disrupted the activation of the temporary buffer process, and no amount of dopamine receptor activation improved their ability to focus.
Cooper said this result matched what they already knew about how the brains of addicts behave, “it all fits together”, he said, explaining that:
“This makes sense because we know from human and animal models of addiction, when a decision using working memory has to be made, brain imaging shows a deficit in the same area of the brain we looked at.”
Their next step is to identify the exact ion channel that holds and regenerates a memory trace; they hope this leads to new drugs and genetic tools that will help to enhance memory capacity in decision making, for example by helping drug addicts consider the consequences of impulsive behaviour.
“If we can identify and manipulate the molecular components of memory, we can develop drugs that boost the ability to maintain this memory trace to hopefully allow a person to complete tasks without being distracted,” said Cooper.
“For the person addicted to drugs, we could strengthen this part of the brain involved with decision-making, allowing them to ignore impulses and weigh negative consequences of their behavior before they abuse drugs,” he explained.
The study was sponsored by the National Institute on Drug Abuse; National Alliance for Research on Schizophrenia and Depression; the Alexander S. Onassis Public Benefit Foundation; and the Department of Veterans Affairs.
“Dopamine modulates an mGluR5-mediated depolarization underlying prefrontal persistent activity.”
Kyriaki Sidiropoulou, Fang-Min Lu, Melissa A Fowler, Rui Xiao, Christopher Phillips, Emin D Ozkan, Michael X Zhu, Francis J White, Donald C Cooper.
Nature Neuroscience Published online 25 Jan 2009.
doi: 10.1038/nn.2245
Sources: UT Southwestern, journal abstract.
Written by: Catharine Paddock, PhD