| Study in Flies 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.1
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
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
1Yu 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.