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Discovery Of Brain's Memory
'Buffer' In Single Cells
Individual nerve cells in the front part of the brain can
hold traces of memories on their own for as long as a minute and
possibly longer,researchers at UT Southwestern Medical Center have found |
The study, available
online and appearing in the February issue of Nature Neuroscience,
is the first to identify the specific signal that establishes
nonpermanent cellular memory and reveals how the brain holds temporary
information. It has implications for addiction, attention disorders and
stress-related memory loss, said Dr. Don Cooper, assistant professor of
psychiatry at UT Southwestern and senior author of the study conducted
in mice.
Researchers have known that permanent memories are stored when the
excitatory amino acid glutamate activates ion channels on nerve cells in
the brain to reorganize and strengthen the cells' connections with one
another. But this process takes minutes to hours to turn on and off and
is too slow to buffer, or temporarily hold, rapidly incoming
information.
The researchers found that rapid-fire inputs less than a second long
initiate a cellular memory process in single cells lasting as long as
minute, a process called metabotropic glutamate transmission. This
transmission in the most highly evolved brain region holds
moment-to-moment information.
These cellular findings have implications for how the human brain stores
rapidly changing information, like the temporary memory a card shark
uses when counting cards in a game of Black Jack and, as casinos have
figured out, it is the memory that is most sensitive to the disruptive
effects of alcohol and noisy distractions, Dr. Cooper said.
"It's more like RAM [random access memory] on a computer than memory
stored on a disk," Dr. Cooper said. "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."
The researchers identified in mice a specific metabotropic glutamate
receptor called mGluR5 that, when turned on, starts a signaling cascade
using calcium to hold a memory trace. This fast, short-term memory
process happens inside individual cells; with long-term memory,
additional proteins cause slow reorganization between cells in a network
to establish a permanent memory.
Researchers examined brain cells from mice using nanoscale electrodes to
measure the memory formation process.
To further understand how this short-term memory process relates to
addiction, researchers applied the neurochemical dopamine to the memory
buffer nerve cells. Dopamine is normally needed at an optimal level for
an individual to focus attention and engage in fast decision-making
memory, but drugs of abuse overload the brain with a surge of dopamine.
In the study, researchers found that an experimental drug that activates
a specific type of dopamine receptor "focused" the nerve cells, making
the memory trace less susceptible to distraction.
When researchers employed an animal model of drug addiction using
cocaine, they also found that repeated exposure to addictive levels of
cocaine reduced memory trace activation in the memory buffer cells. When
researchers then activated dopamine signaling in the "addicted" animals,
essentially adding more dopamine to their systems, no focusing effect
was observed.
"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," Dr.
Cooper said. "It all fits together."
Researchers next plan to identify the ion channel responsible for
holding and regenerating a memory trace. Their goal is to develop new
pharmacological and genetic tools that will allow them to manipulate and
possibly expand decision-making memory capacity.
"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," Dr. Cooper said. "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."
Other researchers from UT Southwestern involved in the study in Dr.
Cooper's laboratory were Dr. Fang-Min Lu, assistant instructor of
psychiatry; Melissa Fowler, a graduate student in psychiatry;
Christopher Phillips, a medical student; and Emin Ozkan, student
research assistant in physiology. Lead author Kyriaki Sidiropoulou from
Rosalind Franklin University of Medicine and Science's Chicago Medical
School and researchers from Ohio State University also participated in
the study.
The study was funded 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.
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