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Subject: STUDY ALLOWS RESEARCHERS TO VISUALIZE FORMATION OF A MEMORY


U.S. Department of Health and Human Services

NATIONAL INSTITUTES OF HEALTH

NIH News

National Institute of Neurological Disorders and Stroke
http://www.ninds.nih.gov/

EMBARGOED FOR RELEASE
Wednesday, May 12, 2004
12:00 p.m. ET

CONTACT:
Natalie Frazin
or Paul Girolami
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STUDY ALLOWS RESEARCHERS TO VISUALIZE FORMATION OF A MEMORY

For the first time, researchers have used a technique
called optical imaging to visualize changes in nerve connections when
flies learn. These changes may be the beginning of a complex chain of
events that leads to formation of lasting memories. The study was funded
in part by the NIH's National Institute of Neurological Disorders and
Stroke (NINDS) and appears in the May 13, 2004, issue of "Neuron".*

Scientists have long been captivated by the questions of
how memories form and how they are represented in the
brain. The answers to these questions may help researchers understand
how to treat or prevent memory problems, drug addiction, and other human
ailments. Thousands of changes in gene expression, neuron formation,
nerve signaling, and other characteristics may be involved in the
formation of just a single memory. Scientists refer to any learning-
induced change in the brain as a "memory trace."

In the new study, Ronald L. Davis, Ph.D., and colleagues at Baylor
College of Medicine in Houston developed fruit flies with special genes
that caused the flies' neuronal connections to become fluorescent during
nerve signaling (synaptic transmission). They then exposed the flies to
brief puffs of an odor while they received a shock. This caused them to
learn a new association between the odor and the shock - a type of
learning called classical conditioning.

Using a high-powered microscope to watch the fluorescent signals in
flies' brains with as they learned, the researchers discovered that a
specific set of neurons, called projection neurons, had a greater number
of active connections with other neurons after the conditioning
experiment. These newly active connections appeared within 3 minutes
after the experiment, suggesting that the synapses which became active
after the learning took place were already formed but remained "silent"
until they were needed to represent the new memory. The new synaptic
activity disappeared by 7 minutes after the experiment, but the flies
continued to avoid the odor they associated with the shock.

This is the first time that optical imaging has been used
to visualize a memory trace, Dr. Davis says. "It's
phenomenally powerful, like a movie appearing in front of
you," he adds. The study suggests that the earliest representation of a
new memory occurs by rapid changes - "like flipping a switch" - in the
number of neuronal connections that respond to the odor, rather than by
formation of new connections or by an increase in the number of neurons
that represent an odor, he adds.

The fact that the flies continued to show a learned
response even after the new synaptic activity waned
suggests that other memory traces found at higher levels in
the brain took over to encode the memory for a longer
period of time, Dr. Davis suggests. If so, the rapid
changes of nerve transmission that the researchers saw may
be the all-important switch that initiates the formation of
new memories.

This research suggests a previously unknown mechanism for
how memories are formed, Dr. Davis says. While this study looked only at
learning related to odors, this newly identified process may be at work
in many other kinds of learning as well. It is likely that these or
similar mechanisms are important for memory in humans and other animals,
he adds.

"This is a remarkable study which uses molecular genetic approaches to
visualize memory formation in a living organism. It demonstrates that,
in this model system, short term memory involves the recruitment of new
synaptic connections into pre-existing ensembles of synapses. It will be
critical to determine whether similar principles control memory
formation in higher organisms," says Robert Finkelstein, Ph.D., a
program director at NINDS.

The researchers now plan to put fluorescent genes into a variety of
other neurons of the brain in order to determine which ones respond to
different kinds of stimuli. This will allow them to learn how the
changes they identified affect higher-level neurons. They also hope to
begin studying similar mechanisms in other animal models, such as mice.

The NINDS is a component of the National Institutes of
Health within the Department of Health and Human Services
and is the nation's primary supporter of biomedical
research on the brain and nervous system.

--------------------------------------------

*Yu D, Ponomarev A, Davis RL. "Altered representation of
the spatial code for odors after olfactory classical
conditioning: memory trace formation by synaptic
recruitment." 'Neuron', May 13, 2004, Vol. 42, No. 3, pp. 437-449.

##

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http://www.nih.gov/news/pr/may2004/ninds-12.htm

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