MANIPULATING MEMORY WITH LIGHT
Just look into the
light: not quite, but researchers at the UC Davis Center for Neuroscience and
Department of Psychology have used light to erase specific memories in mice,
and proved a basic theory of how different parts of the brain work together to
retrieve episodic memories
Optogenetics,
pioneered by Karl Diesseroth at Stanford University, is a new technique for
manipulating and studying nerve cells using light. The techniques of
optogenetics are rapidly becoming the standard method for investigating brain
function.
Kazumasa Tanaka, Brian
Wiltgen and colleagues at UC Davis applied the technique to test a
long-standing idea about memory retrieval. For about 40 years, Wiltgen said,
neuroscientists have theorized that retrieving episodic memories -- memories
about specific places and events -- involves coordinated activity between the
cerebral cortex and the hippocampus, a small structure deep in the brain.
"The theory is
that learning involves processing in the cortex, and the hippocampus reproduces
this pattern of activity during retrieval, allowing you to re-experience the
event," Wiltgen said. If the hippocampus is damaged, patients can lose
decades of memories.
But this model has
been difficult to test directly, until the arrival of optogenetics.
Wiltgen and Tanaka used
mice genetically modified so that when nerve cells are activated, they both
fluoresce green and express a protein that allows the cells to be switched off
by light. They were therefore able both to follow exactly which nerve cells in
the cortex and hippocampus were activated in learning and memory retrieval, and
switch them off with light directed through a fiber-optic cable.
They trained the mice
by placing them in a cage where they got a mild electric shock. Normally, mice
placed in a new environment will nose around and explore. But when placed in a
cage where they have previously received a shock, they freeze in place in a
"fear response."
Tanaka and Wiltgen
first showed that they could label the cells involved in learning and
demonstrate that they were reactivated during memory recall. Then they were
able to switch off the specific nerve cells in the hippocampus, and show that
the mice lost their memories of the unpleasant event. They were also able to
show that turning off other cells in the hippocampus did not affect retrieval
of that memory, and to follow fibers from the hippocampus to specific cells in
the cortex.
"The cortex can't
do it alone, it needs input from the hippocampus," Wiltgen said.
"This has been a fundamental assumption in our field for a long time and
Kazu’s data provides the first direct evidence that it is true."
They could also see
how the specific cells in the cortex were connected to the amygdala, a
structure in the brain that is involved in emotion and in generating the
freezing response.
Co-authors are
Aleksandr Pevzner, Anahita B. Hamidi, Yuki Nakazawa and Jalina Graham, all at
the Center for Neuroscience. The work was funded by grants from the Whitehall
Foundation, McKnight Foundation, Nakajima Foundation and the National Science
Foundation.
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