In a remarkable demonstration of the curative power
of memory, published in Nature, scientists have
established that artificial reactivation of memories
stored during a positive experience can suppress the
effects of stress-induced depression.
The research, conducted by scientists at the
RIKEN-MIT Center for Neural Circuit Genetics, a
joint collaboration of RIKEN Brain Science Institute
in Japan and MIT, shows how positive and negative
memories interact in mood disorders, and provides a
specific brain circuit for future clinical
interventions.
A magnified image of a mouse brain showing memory
cells (red) that can be turned ‘on’ and ‘off’ using
light delivered by a fiber optic cable (black). ©
2014 Susumu Tonegawa, RIKEN–MIT Center for Neural
Circuit Genetics
The research, conducted in the laboratory of RIKEN
Brain Science Institute Director Susumu Tonegawa, an
MIT Professor and 1987 Nobel Laureate for the
discovery of antibody diversity, tackles the
long-standing question of whether a positive memory
can overwrite a negative one.
To answer the question, the research team used
genetic engineering to create mice in which memory
cells from a brain area called the dentate gyrus
(DG) could be tagged while memories formed, and
later reactivated with a blue light-emitting optical
fiber implanted in the DG. The team could then turn
on memory cells created during previous experiences.
To test the system, male mice were given a positive
experience—exposure to a female mouse—and formed a
memory of the event. They were then exposed to a
stressful experience that led to a depression-like
state. While they were depressed, light was used to
stimulate the DG of some mice and reactivate the
memory cells for the positive experience.
Surprisingly, this resulted in a robust recovery
from the depressed state. Mapping the brain circuit
for this effect revealed two other brain areas—the
BLA and NAcc—that cooperate with the DG.
To examine whether this type of recovery from
depression can include persistent changes in brain
circuitry that remain even in the absence of light
stimulation, the researchers supplied chronic light
therapy to the DG over 5 days, ensuring sustained
reactivation of the positive memories. Mice who
received this therapy were resilient to the negative
effects of stress-induced depression, suggesting
that memory storage of positive experiences in the
DG can be used to suppress or overwrite the damaging
effects of stress on behavior, a new concept in mood
control.
The findings have important implications for the
persistence of memory in coping with stress and
depression. The interaction of positive and negative
experiences and their corresponding memories is
poorly understood, but the findings open a path to
new approaches in mood disorder therapy that might
be helpful for patients in the future. The authors
say it is too early to conclude whether positive
memories in general can mitigate the effects of
stressful depression. However, it is clear that DG
cells are promising targets for therapeutic
approaches to maladaptive mood states.
See also:
Higher glucose levels associated with lower memory
and reduced hippocampal microstructure (2013-11-05)
Enzyme Can Alter Long-Term Memories (26/03/2012)
A neural network in the brain controls how
associations are made between events separated in
time (2014-07-01)
Sticky synapses can impair new memories by holding
on to old ones (2014-05-27)
Neuroscientists Find Brain Activity May Mark the
Beginning of Memories (2014-04-22)
Making memories last (06/02/2012)
For more information
Steve Ramirez, Xu Liu, Christopher J. MacDonald,
Anthony Moffa, Joanne Zhou, Roger L. Redondo &
Susumu Tonegawa
"Activating positive memory engrams suppresses
depression-like behavior"
Nature 2015,
doi: 10.1038/nature14514
RIKEN Institute
MDN |