University of California, Davis
December 13, 2012
Memories are made of this, the song says. Now neuroscientists have for the first time shown individual mouse brain cells being switched on during learning and later reactivated during memory
recall. The results are published Dec. 13 in the journal Current Biology.
We store episodic memories about events in our lives in a part of a brain called the hippocampus, said Brian Wiltgen, now an assistant professor at the Center for Neuroscience and
Department of Psychology at the University of California, Davis. (Most of the work was conducted while Wiltgen was working at the University of Virginia.) In animals,
the hippocampus is important for navigation and storing memories about places.
"The exciting part is that we
are now in a position to answer a fundamental question about memory,"
Wiltgen said. "It's been assumed for a long time that the hippocampus is
essential for memory because it drives reactivation of neurons (nerve cells) in
the cortex. The reason you can remember an event from your life is because the
hippocampus is able to recreate the pattern of cortical activity that was there
at the time."
According to this model, patients
with damage to the hippocampus lose their memories because they can't recreate
the activity in the cortex from when the memory was made. Wiltgen's mouse
experiment makes it possible to test this model for the first time.
"We can now do a nice test of
hippocampal function," Wiltgen said.
Current thinking is that learning
activates a group of neurons that undergo changes, making new connections with
each other to store the memory. Retrieving the memory reactivates the network.
Researchers working with human
subjects, at UC Davis and elsewhere, use imaging techniques such as functional
magnetic resonance imaging to see which areas of the brain are switched on and
off in learning and retrieval. But fMRI cannot pick out an object as small as a
Wiltgen and University of Virginia
graduate student Kaycie Tayler used a genetically modified mouse that carries a
gene for a modified green fluorescent protein. When nerve cells in the mouse
are activated, they produce a long-lived green fluorescence that persists for
weeks, as well as a short-lived red fluorescence that decays in a few hours.
However, the whole system can be
suppressed by dosing the mouse with the antibiotic doxycycline, so Tayler and
Wiltgen could manipulate the point at which they started tagging activated
The mice were put into a new cage
with an unfamiliar odor and given a few minutes to explore. Then they were
given a mild electrical shock through the cage floor. When returned to the cage
a couple of days later, the mice would remember the shock and stay frozen in
When they examined the brains of the
mice, the researchers could see which cells had been activated initially to
form the memory and which were reactivated later to recall it.
About 40 percent of the cells in the
hippocampus that were tagged during initial memory formation were reactivated,
Wiltgen said. There was also reactivation of cells in parts of the brain cortex
associated with place learning and in the amygdala, which is important for
There was no evidence of
reactivation when the mice were tested in a new environment that they did not
remember, Wiltgen said.
The researchers also looked at
whether reactivation changed as memories got older. Over several weeks,
reactivation in the cortex and parts of the hippocampus remained stable, but it
decreased in other brain regions like the amygdala.
In future work, Wiltgen's team plans
to examine the role of the hippocampus and other brain regions in forming memories
and explore new ways to activate or block memories.
Other authors of the paper are
Kazumasa Tanaka at the University of Virginia
and Leon Reijmers at Tufts University School of Medicine.
The work was supported by the
McKnight Foundation, the National Science Foundation and the Nakajima
About UC Davis
For more than 100 years, UC Davis
has engaged in teaching, research and public service that matter to California and transform
Located close to the state capital,
UC Davis has more than 33,000 students, more than 2,500 faculty and more than
21,000 staff, an annual research budget of nearly $750 million, a comprehensive
health system and 13 specialized research centers. The university offers
interdisciplinary graduate study and more than 100 undergraduate majors in four
colleges -- Agricultural and Environmental Sciences, Biological Sciences,
Engineering, and Letters and Science. It also houses six professional schools
-- Education, Law, Management, Medicine, Veterinary Medicine and the Betty
Irene Moore School of Nursing.
* Brian Wiltgen, Center for
Neuroscience, (530) 754-9137, email@example.com
* Andy Fell, UC Davis News Service,
(530) 752-4533, firstname.lastname@example.org
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