It may turn out the reason some people grow increasingly
forgetful as they age is less about how old they are and more
about subtle changes in the way the brain files memories and
makes room for new ones - differences perhaps better blamed on
patterns of cell-to-cell communication than the number of
birthday candles decorating the cake.
A researcher with the
McKnight Brain Institute of the University of Florida has found
that rats become forgetful because a routine part of the memory
process falls out of kilter, no matter their ages.
This change seems to be related to the chemicals necessary
for brain cells to communicate with each other. The findings,
published this month in the online edition of Neurobiology of
Learning and Memory, expand the possibility that drugs or
therapies could be developed to tune up the brain's memory
mechanisms.
"Aging is associated with an increased rate of forgetting,"
said Thomas Foster, Ph.D., the Evelyn F. McKnight chair for
brain research in memory loss at the College of Medicine. "My
work indicates that the problem may be a slight shift in a
normal forgetting mechanism."
Scientists believe a memory forms when communication
increases between brain cells called neurons. During memory
formation, signals jump across narrow gaps between cells called
synapses, and this output becomes increasingly larger.
But for this activity to efficiently create a memory, it
helps if signaling decreases among less-involved neurons. It's
like quieting other people in the room so you can have a phone
conversation. Scientists call the process of decreasing the
signal at less-involved synapses "long-term depression," or LTD.
"This is a normal process that helps with the sculpting of
memory," Foster said. "After all, we do not remember everything
in perfect detail and we would not want to. This same mechanism
probably is used to clear the brain circuits and make them ready
to be used the next day. However, this mechanism in excess may
lead to rapid forgetting as seen during brain aging."
Foster's lab group used aged and young rats to examine the
relationships between LTD, aging and memory. The animals were
trained to find a hidden platform to climb out of a pool of
water - something they learned quickly with repetition.
When the researchers examined the animals' neurons and used a
slow, weak electrical signal to make the synapses less sensitive
- an effort to squelch or depress the cellular communication -
he found that the samples from younger animals and older animals
that had the highest memory scores throughout their lives were
more resistant to the interference. However, aged animals with
impaired memories displayed what was termed as "robust long-term
depression."
Going back to the phone call example, not only did the rest
of the room get quieter, the callers did, too. The assumption is
if a memory is encoded by making synapses stronger, then memory
can be disrupted by something that weakens those connections.
"When we see someone we know or perhaps even ourselves
becoming more forgetful, we now know that this is not an
inevitable process," Foster said. "Further, as we begin to
understand the mechanisms of memory, it becomes possible to
predict promising targets for therapeutic strategies aimed at
postponing or alleviating age-related memory impairment."
Foster said it will be important to understand whether a
change in cellular signaling is necessary to enable new memories
to be formed by discarding old ones.
"The basic gist is that information storage requires a
balance between mechanisms that make synapses stronger and
weaker," said Mark F. Bear, Ph.D., director of the Picower
Institute for Learning and Memory at the Massachusetts Institute
of Technology, who was not involved with the research. "In aging
and disease, if that balance is disrupted to favor LTD, the
unchecked synaptic weakening leads to memory loss. The good news
is we are developing a good understanding of these mechanisms,
and that will help us find ways to protect memory."
Foster's work was supported by the National Institutes of
Health and an Evelyn F. McKnight Brain Research grant.
Foster’s work was supported by the
National
Institutes of Health and an Evelyn F.
McKnight Brain Research grant.