Scientists have directly demonstrated in rats that one
area of the brain can support the creation of memories by
changing nerve cell firing patterns in another part of the
brain, aiding the animal's efforts to predict the outcome
of an action based on past experience and act on that
prediction.
The process, one scientist says, is something like
what happens when a comic strip figure sees something and
is immediately reminded of something else.
"I like to think of it like a cartoon character with a
thought bubble over his head," explained Geoffrey
Schoenbaum, until last week an associate
psychological and brain
sciences research scientist in the Krieger School of
Arts and Sciences. "There's a neural representation of
something in the mind that is invoked by the environment
but not yet present in the environment."
This comparison led to a cartoon for the cover of the
Aug. 28 issue of the journal Neuron, where the study
is published. In the drawing, a rat stands at a fork in the
road, consults a map and thinks, in a thought bubble, of
cheese. The cheese isn't present in the rat's surroundings,
but the rat knows through past experience that choosing the
right path could lead him to it.
Schoenbaum, now an assistant professor of anatomy and
neurobiology at the University of Maryland School of
Medicine, directly observed the brain mechanisms involved
in such predictive associations by using implanted
electrodes to record the activity of individual nerve cells
in two regions of the brain, the amygdala and the
orbitofrontal cortex.
In earlier studies, the researchers had demonstrated
that nerve cells in these two connected brain regions
changed their firing patterns to reflect the associations
between cues and outcomes during learning.
For the study published in Neuron, they examined how
changes in neural activity in amygdala might be supporting
changes in the orbitofrontal cortex. To do this, they
recorded brain cell activity in the orbitofrontal cortex
from two groups of rats: a normal group and a group with
chemical lesions to their amygdalas. Prior to the
experiments, the rats' water sources were taken away for a
time to make them thirsty. In repeated trials, scientists
would then link odors to the appearance a few moments later
of either desirable drinking water, which was laced with
sugar, or undesirable drinking water, laced with quinine
and unpalatable even to thirsty rats.
"We found that the patterns that normally develop in
orbitofrontal cortex when rats are smelling the odor cue,
which appear to reflect information about the predicted
outcome, failed to appear in rats with amygdala lesions."
Schoenbaum said.
As normal rats learned to use the odor cues to predict
the type of fluid they would receive, the orbitofrontal
cortex activity patterns eventually began appearing much
more quickly, starting in response to the odor cue--before
the fluid was given. In experimental rats, though, early
activation of orbitofrontal cortex patterns never
occurred.
"This is the most direct evidence yet for how one
brain system, the amygdala, controls the way
representations are made in another directly connected
system," said Michela Gallagher, chairman of the Department
of Psychological and Brain Sciences at Johns Hopkins and a
co-author of the Neuron paper. "We have long
suspected the existence of this network because the
amygdala is necessary for the type of learning process we
studied, but we have only recently begun to examine how
these interactions occur and shape how the world around us
is represented in the brain."
Schoenbaum noted that the rats with lesioned amygdalas
still learned to avoid the undesirable drinking water,
apparently through other mechanisms that back up those
normally present in the connection between the amygdala and
the orbitofrontal cortex. He added that scientists can't
yet say for certain what the brain cell activity patterns
they identified in the orbitofrontal cortex represent--a
mental picture of the water to come, for example; or of the
gratification or lack of gratification the water will
produce; or something else entirely.
Schoenbaum hopes to apply data from the study to
research into brain changes brought on by addiction. He's
interested in investigating the possibility that addiction
may damage or impede the connection between the amygdala
and the orbito-frontal cortex, impairing an addict's
ability to assess adequately the consequences of his or her
actions. Gallagher will use data from the study to aid her
studies of how aging can affect memory functions.
This research was supported by grants from the
National Institute of Mental Health and the National
Institute on Aging. Other authors on the paper were Barry
Setlow and Michael Saddoris.