Tuesday, June 16,
2009
Scientists have long thought that processes occurring during sleep
were responsible for cementing the salient experiences of the day
into long-term memories. Now, however, a study of scampering rats
suggests that the mechanisms at work during sleep are also active
while the animals are awake -- and that they encode events more
accurately.
The finding has significant implications for understanding the way
the brain learns and remembers, the researchers say. Among other
things, it could offer insights into, and possible strategies for
combating, post traumatic stress disorder.
The study is reported in the June 14 online edition of the July
2009 issue of "Nature Neuroscience."
As people – and rats – go about their daily lives, they receive a
ceaseless stream of sensory stimuli that is taken up by neurons, or
nerve cells, in the eyes, ears, nose, taste buds and skin. This
information is encoded in the neurons and transmitted along neural
pathways into various processing centers in the brain that assess
the information and decide what to do with it.
The current study focused on the neural activity in a region of the
brain known as the hippocampus, a horseshoe-shaped structure
responsible for encoding all spatial and event memories of daily
life. It is thought that the hippocampus rapidly encodes all
experiences in highly plastic, or flexible, neural circuits within
it and then, later, reactivates those neural representations of the
experience that are deemed significant, allowing their patterns to
be engrained in less-plastic hippocampal-neocortical circuits where
they are stored as long-term memory.
"The accepted dogma has been that one learns something while awake
– the process of rapid encoding -- and that later, while asleep,
one replays the memory over and over again until it is cemented, or
consolidated, in circuits throughout the brain," says the senior
author of the study, Loren M. Frank, PhD, assistant professor of
physiology and member of the W.M. Keck Center for Integrative
Neuroscience at UCSF.
But this theory has not explained what happens if one does not
sleep right after an experience, Frank notes. "We've known the
memory doesn't necessarily go away but we haven't known what
supported memory formation in such cases."
Scientists have known that rats, during brief pauses in movement as
they scurry about their day, replay their immediate experience.
This allows them to learn the experience in the short term and to
integrate knowledge about it with past experiences in order to make
decisions about next steps. The process may even prompt changes in
synaptic connections between neurons that begin the process of
laying down long-term memories.
However, until now, scientists have thought that awake replay of
events was limited to the immediate past.
In the current study, Frank and first author Mattias P. Karlsson,
PhD, a graduate student in Frank's lab, studied rats' neural replay
in several settings – while they sniffed and explored two different
places, one familiar, one novel -- and while they dozed in a rest
box. In each case, the scientists recorded the activity of
individual neurons in the hippocampus as they fired, one after the
other, as the hippocampus "reflected" back on their experience in
each place.
The first surprise was that in both awake settings there was a near
constant replay of events that had taken place in the past – some
20 to 30 minutes earlier. These replay events were seen in peppered
bursts of activity present during the brief pauses the animals made
repeatedly during their exploration.
"These past experiences were popping up over and over again – every
couple of seconds," says Frank.
More surprisingly, the awake replay often involved events that had
occurred in a different setting than the ones the animals were in
during replay. In fact, 40 to 50 percent of the replays of past
experience the animals had as they moved through the familiar place
involved events they had experienced in the novel place.
"These findings suggest that elements of past experience are
constantly being reactivated as we go about our daily lives,
independent of incoming sensory information," says Frank.
Provocatively, the neural replay of past experiences detected in
the animals while they slumbered was significantly less accurate
than when they were awake. One possible explanation, says Frank, is
that the replay during a sleep-like state may not be intended to be
a perfect reenactment of what occurred. Evidence suggests that
sleep is a time for making connections. "Maybe during sleep the
brain is sort of relaxing, saying 'I'm not going to be completely
true to the experience I just had. I'm going to wander around and
explore and make new connections.'"
The team's next step is to determine if awake replay of past
experiences is essential for learning, a question they plan to
explore by electrically interrupting, or "turning off," discrete
segments of the replay process as the animals scurry about their
day. The question we will ask, says Frank, is "can we stop the
learning?"
More broadly, the team wants to see if the awake replay of past
experiences seen in the hippocampus is driving memory processes
across the brain. "We should be able to see neural signatures of
past experience come up in the prefrontal cortex -- another region
of memory storage -- when these signatures come up in the
hippocampus," he says.
Ultimately, says Frank, "We'd like to explore whether we can
control these replay processes in a subtle way. Can we, for
example, pick out certain kinds of neural patterns that we allow to
happen and not others. Could we prevent or enhance the creation of
some memories and not of others?"
This possibility poses the question of whether it would be possible
to prevent the traumatic memories associated with post traumatic
stress syndrome or to stop them. "The question for me has always
been-- why do these experiences have such a lasting impact? This is
the first time I've found something that might make sense of all of
that," Frank adds.
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University of California - San Francisco
Thanks to University of California
- San Francisco for this article.