Two
studies, led by University of Texas Southwestern (UTSW) researchers, shed new
light on how the brain encodes time and place into memories. The findings, published recently in “PNAS”
(Proceedings of the National Academy of Sciences – in the US) and “Science”,
not only add to the body of fundamental research on memory, but could
eventually provide the basis for new treatments to combat memory loss from
conditions such as traumatic brain injury or Alzheimer's disease.
About a decade ago, a group of neurons known as
"time cells" was discovered in rats.
These cells appear to play a unique role in recording when events take
place, allowing the brain to correctly mark the order of what happens in an
episodic memory.
Located in the brain's hippocampus, these cells show
a characteristic activity pattern while the animals are encoding and recalling
events, explains Bradley Lega, M.D., associate professor of neurological
surgery at UTSW and senior author of the PNSD study. By firing in a reproducible sequence, they
allow the brain to organize when events happen, Lega says. The timing of their firing is controlled by 5
Hz brain waves, called theta oscillations, in a process known as precession.
Lega investigated whether humans also have time cells
by using a memory task that makes strong demands on time-related
information. Lega and his colleagues
recruited volunteers from the Epilepsy Monitoring Unit at UT Southwestern's
Peter O'Donnell Jr. Brain Institute, where epilepsy patients stay for several
days before surgery to remove damaged parts of their brains that spark
seizures. Electrodes implanted in these
patients' brains help their surgeons precisely identify the seizure foci, and
also provide valuable information on the brain's inner workings, Lega says.
While recording electrical activity from the
hippocampus in 27 volunteers' brains, the researchers had them do "free
recall" tasks that involved reading a list of 12 words for 30 seconds,
doing a short math problem to distract them from rehearsing the lists, and then
recalling as many words from the list as possible for the next 30 seconds. This task requires associating each word with
a segment of time (the list it was on), which allowed Lega and his team to look
for time cells. What the team found was
exciting: Not only did they identify a
robust population of time cells, but the firing of these cells predicted how
well individuals were able to link words together in time (a phenomenon called
temporal clustering). Finally, these
cells appear to exhibit phase precession in humans, as predicted.
"For years scientists have proposed that time
cells are like the glue that holds together memories of events in our
lives," according to Lega.
"This finding specifically supports that idea in an elegant
way."
In the second study in “Science”, Brad Pfeiffer,
Ph.D., assistant professor of neuroscience, led a team investigating place
cells, a population of hippocampal cells in both animals and humans that
records where events occur. Researchers
have long known that as animals travel a path they've been on before, neurons
encoding different locations along the path will fire in sequence much like
time cells fire in the order of temporal events, Pfeiffer explains. In addition, while rats are actively
exploring an environment, place cells are further organized into
"mini-sequences" that represent a virtual sweep of locations ahead of
the rat. These radar-like sweeps happen
roughly 8-10 times per second and are thought to be a brain mechanism for
predicting immediately upcoming events or outcomes.
Prior to this study, it was known that when rats
stopped running, place cells would often reactivate in long sequences that
appeared to replay the rat's prior experience in the reverse. While these "reverse replay" events
were known to be important for memory formation, it was unclear how the
hippocampus was able to produce such sequences.
Indeed, considerable work had indicated that experience should strengthen
forward, "look ahead" sequences but weaken reverse replay events.
To determine how these backward and forward memories
work together, Pfeiffer and his colleagues placed electrodes in the hippocampi
of rats, then allowed them to explore two different places: a square arena and
a long, straight track. To encourage
them to move through these spaces, they placed wells with chocolate milk at
various places. They then analysed the
animals' place cell activity to see how it corresponded to their locations.
Particular neurons fired as the rats wandered through
these spaces, encoding information on place.
These same neurons fired in the same sequence as the rats retraced their
paths, and periodically fired in reverse as they completed different legs of
their journeys. However, taking a closer
look at the data, the researchers found something new: As the rats moved through these spaces, their
neurons not only exhibited forward, predictive mini-sequences, but also
backward, retrospective mini-sequences.
The forward and backward sequences alternated with each other, each
taking only a few dozen milliseconds to complete.
"While these animals were moving forward, their
brains were constantly switching between expecting what would happen next and
recalling what just happened, all within fraction-of-a-second timeframes,"
Pfeiffer says.
Pfeiffer and his team are currently studying what
inputs these cells are receiving from other parts of the brain that cause them
to act in these forward or reverse patterns.
In theory, he says, it might be possible to hijack this system to help
the brain recall where an event happened with more fidelity. Similarly, adds Lega, stimulation techniques
might eventually be able to mimic the precise patterning of time cells to help
people more accurately remember temporal sequences of events. Further studies with "In the past few
decades, there's been an explosion in new findings about memory," he
adds. "The distance between
fundamental discoveries in animals and how they can help people is becoming
much shorter now."