http://web.mit.edu/newsoffice/2007/deja-vu-0607.html
Research deciphers 'déjà-vu' brain mechanics
Deborah Halber, News Office Correspondent
June 7, 2007
Neuroscientists at the Picower Institute for Learning and Memory at
MIT report in the June 7 early online edition of Science that they
have identified for the first time a neuronal mechanism that helps
us rapidly distinguish similar, yet distinct, places. The discovery
helps explain the sensation of déjà vu.
The work could lead to treatments for memory-related disorders, as
well as for the confusion and disorientation that plague elderly
individuals who have trouble distinguishing between separate but
similar places and experiences.
Forming memories of places and contexts in which episodes occur
engages a part of the brain called the hippocampus. Study co-author
Susumu Tonegawa, Picower Professor of Biology and Neuroscience, and
colleagues have been exploring how each of the three hippocampal
subregions--the dentate gyrus, CA1 and CA3--contribute to different
aspects of learning and memory.
Tonegawa, a Howard Hughes Medical Institute investigator and a
frequent world traveler, described his own occasional experience of
finding the airport in a new city uncannily familiar. This occurs,
he said, because of the similarity of the modules--gates, chairs,
ticket counters--that comprise airports worldwide. It is only by
seeking out unique cues that the specific airport can be
identified, he said. "In this study, we have revealed that learning
in the dentate gyrus is crucial in rapidly recognizing and
amplifying the small differences that make each place unique,"
Tonegawa said.
In addition to Tonegawa, authors include Picower Institute research
scientist Thomas J. McHugh; former MIT postdoctoral associate
Matthew W. Jones; Matthew A. Wilson, Picower Scholar and Professor;
and colleagues from the University of California at Los Angeles and
Beth Israel Deaconess Medical Center in Boston.
Overlapping blueprints
In this study, the researchers used a genetically altered mouse to
pinpoint how the dentate gyrus contributes to the kind of pattern
separation involved in telling the difference between new and old
spaces.
Researchers believe that a set of neurons called place cells fire
to provide a sort of blueprint for any new space we encounter. The
next time we see the space, those same neurons fire. Thus we know
when we've been somewhere before and don't have to relearn our way
around familiar turf.
But if we enter a space very similar to one we have seen before, a
new but overlapping set of neurons creates the blueprint. When
there is enough overlap between the two sets, we experience an
eerie feeling of déjà vu--a French phrase that literally means,
"already seen."
As we age, or as neurodegenerative disease such as Alzheimer's
advances, it becomes difficult to form unique memories for similar
yet distinct places and experiences, leading to the confusion that
afflicts some elderly individuals.
Forgetting fear
In experiments with mice genetically engineered to lack a certain
gene in the dentate gyrus, Tonegawa and colleagues pinpointed the
signaling pathway underlying the recall of specific places.
Different sets of mice were placed in two similar chambers, one of
which gave them a mild foot shock. After three days, the mice began
to freeze in fear in both chambers, even the one in which they had
never been harmed.
Within two weeks, the normal mice learned to associate only one
chamber with the foot shocks while recognizing the second as safe.
The genetically engineered mice "had a significant but transient
deficit in their ability to distinguish similar contexts," McHugh
said. "This study shows that plasticity--the ability to change in
response to experience--in the dentate gyrus contributes to spatial
learning and fine-tuning pattern separation."
This work was supported by the National Institute for Mental Health
and the National Institutes of Health.
