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Biological Clock May Shut Down
Long-Term Memory at Night
If you crammed for tests by pulling 'all nighters' in school,
ever wonder why your memory is now a bit foggy on what you learned?
A University of Houston professor may have the answer with his
research on the role of circadian rhythms in long-term learning
and memory. Arnold Eskin, the John and Rebecca Moores Professor
of Biology and Biochemistry at UH, was recently awarded two grants
totaling $2,472,528 from the National Institutes of Health (NIH)
to continue pursuing his investigations of memory formation and
the impact of the biological clock on learning and memory.
Scientists have known for a while that the brain's biological
(or circadian) clock influences natural body cycles, such as sleep
and wakefulness, metabolic rate and body temperature. New research
from Eskin suggests the circadian clock also may regulate the
formation of memory at night. This new research focuses on "Circadian
Modulation of Long-term Memory Formation" and "Long-term Regulation
of Glutamate Uptake in Aplysia," with NIH funding to be disbursed
over four years.
"There is a lot of research going on in memory," Eskin said.
"How do we remember things given that we don't have a camera in
our brain to record events? What changes take place in our brains
that allow us to remember? These grants are about fundamental
learning and memory and about modulation of memory."
For the grant on circadian modulation of long-term memory formation,
Eskin will continue studies based on his data that reveal the
circadian clock modulates several forms of long-term memory in
the marine snail Aplysia.
These studies involved experiments on the defensive reflexes
and feeding responses of Aplysia. Eskin's results showed that
Aplysia form long-term memory when they are trained during the
day but not when they are trained at night. However, short-term
memory of the same behaviors is formed equally well during the
day and night, which might explain why all-night cram sessions
may have helped you get through certain classes in school, but
did not leave you with enough of a lasting impression to become
part of your long-term store of knowledge.
"Somewhere in the molecular circuit, in the neural circuit in
the brain, the biological clock is shutting that circuit off at
a particular time of night. It's shutting molecules down so that
long-term memory can't happen," Eskin said.
Lisa Lyons, a research assistant professor at UH, is the primary
investigator on this grant and is already investigating molecules
involved in memory formation that might be activated during the
day but not at night. NIH funding will help advance the pursuit
of this line of research.
For the grant on long-term regulation of glutamate uptake in
Aplysia, Eskin will focus on the transmitter substance glutamate,
which is involved in memory formation.
"The formation of memory happens at places in the brain called
synapses, where cells 'talk' to one another through the release
of chemicals called transmitter substances," Eskin said. "In order
for transmitters to work, once they are released they have got
to be cleared away so that others can subsequently act. So, there
are not only important mechanisms to release the transmitters,
but also mechanisms to get rid of them, and these are called reuptake
systems."
Eskin is studying glutamate reuptake and glutamate transport
to understand the mechanism or change that takes place at the
synapses of nerve cells (or neurons) that enables people to remember.
In previous research, Eskin found that glutamate transport molecules,
which act as the brain's cleaning crew during learning and memory
formation, actually increase once the long-term memory-forming
process begins. Deficiencies in these glutamate transporters that
affect the strength of connections among the neurons associated
with memory may explain why memory lapses such as forgetting where
you last set down your keys occur.
"This research will provide significant information toward understanding
memory and thus diseases that affect memory," Eskin said.
With the potential to shed light upon neurodegenerative diseases
such as Alzheimer's – marked by a loss of brain function due
to the deterioration of neurons – studying these nerve cells
could one day take this research from helping you be better able
to find your glasses to providing relief from a debilitating illness.
"At the end of the day, we can't make memory better or improve
it unless we understand how memory works and is modulated," he
said. "That's what this research is all about."
He is currently completing the last year of another NIH-funded
grant on "Glutamate Transport Regulation and Synaptic Plasticity"
that complements these two new grants, but investigates the role
of glutamate uptake in associative learning in mammals. This research
project on mammals represents a great example of traslational
research in which basic findings in a simple system (i.e. Aplysia)
were quickly applied to a higher organism (i.e. mammals). They
found that glutamate transport increased in the brains of mammals
during learning as also found in Aplysia. (See related release
at http://www.uh.edu/admin/media/nr/2002/032002/eskinlearning.html.)
Coming to UH more than 25 years ago, Eskin guided the merger
of two departments into what is now the Department of Biology
and Biochemistry in the College of Natural Sciences and Mathematics.
As department chair from 1994 to 2000, Eskin tripled research
grants to approximately $6 million per year and developed the
department's research foci of neuroscience, the biological clocks
and infectious disease. The author or co-author of more than 150
publications, he has received numerous honors, including the Esther
Farfel Award, the university's highest faculty honor. He is the
only faculty member to receive both the Farfel Award and the Moores
Professorship in the same year. Eskin earned his bachelor's degree
in physics from Vanderbilt University and his doctorate in zoology
from the University of Texas.
UH's Biological Clocks Program is one of the world's leading
centers for circadian rhythms research, with five laboratories
and a team of more than 30 scholars. In addition to Eskin, the
group is led by four other tenured faculty members in the biology
and biochemistry department – Associate Professor Gregory M.
Cahill, Professor Stuart Dryer, Professor Paul Hardin and Professor
Michael Rea.
Reference
Source 131
March 2, 2005
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