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07/11/2007
Capturing the Moment
I haven’t yet received my copy of Science that contains the
article on which so much media attention was lavished last week.
I’m talking, of course, about the work purporting to show that
men talk just as much as women. While I haven’t seen the
article, media accounts indicate that the study involved college
students as the subjects. If this is correct, it seems to me there is
much more work that needs to be done. The subjects were
young. What about more mature men and women? Does
marriage affect the talkativeness of either sex? As memory
fades, is there more or less talking?
A few weeks ago, I attended a lecture on memory and
Alzheimer’s disease. Slowly, the questions as to how
Alzheimer’s shuts down memory and how the memory loss can
be slowed down or prevented are being answered. On the other
hand, an article by Joe Tsien in the July Scientific American
looks at how memories are stored. Following up on some of this
work, I visited a CalTech Web site on memory that cites a quote
from Tennessee Williams’ novel “The Milk Train Doesn’t Stop
Here Anymore”. “Has it ever struck you, Connie, life is all
memory except for the one present moment that goes by you so
quick you hardly catch it going?” This seems to me a truly
profound insight by Williams. As you read this word, it would
make no sense without your memory of the words that preceded
it. Life makes no sense without memory.
Tsien and his group at Princeton University made headlines back
in 1999 with their genetic tinkering that yielded a strain of
unusually smart mice. The strain was termed Doogie, after the
exceptionally bright, youthful doctor in the TV series “Doogie
Howser, M.D.” The Doogie mice were quicker learners and
could remember tasks longer than their normal colleagues. In his
article titled “The Memory Code”, Tsien, now at Boston
University, describes work on such mice to further our
understanding of how memories are stored in the brain.
The trick is to monitor the activities of hundreds of neurons of
mice that are awake and unfettered, a feat that has been
accomplished in monkeys. The problem with mice is that their
brains are much smaller, about the size of a peanut. Tsien says
that previously only 20-30 neurons had been monitored
simultaneously in mice. However, he and a postdoc, Longnian
Lin, came up with a device allowing the recording of as many as
260 individual cells in the so-called CA1 region of the
hippocampus in the mouse brain. This CA1 region is heavily
involved in the formation of memory in us humans as well as in
mice.
Having developed a means of recording these neurons, how to
measure memory formation and what do you want the mice to
remember? Well, what sort of memories stick with us for the
rest of our lives? Tsien cites 9/11 as one example; those of us in
the metropolitan New York area will certainly never forget the
searing events of that day. Tsien apparently had a personal
memorable experience falling 13 stories in Disney’s Tower of
Terror. He and his group decided that the mouse equivalent of
such “startling events” would be of the type that a mouse would
likely remember.
Accordingly, Tsien and his team simulated (a) an earthquake by
shaking a container holding the mouse, (b) an owl attack from
the sky by a sudden puff of air on the mouse’s back and (c) the
Tower of Terror by a short free fall in an “elevator”, which
initially was simply a cookie jar. The workers subjected the
mice to each of these startling events while monitoring the CA1
cells. The recording device registered the firing or lack of it in
each of the 200 or more cells during the event and when the mice
were at rest.
After repeated runs involving rest periods and the startling
events, Tsien and another postdoc, Remus Osan, analyzed the
data using software designed to recognize patterns in data. Tsien
doesn’t go into details of the data analysis but does say that they
could reduce all that data from the 260 or so neurons to some sort
of 3-dimensional x-y-z plot. In the 3-D plot, the data cluster in 4
distinctly separate “bubbles” of activity for rest, air puff (owl),
earthquake (shaking) and drop (Tower of Terror).
If they follow the patterns in time the workers can see the pattern
from the rest bubble spread out to, for example, the puff bubble
and then return as the mouse rests. They also see the startling
event bubble patterns return on occasion in the mouse brain some
time after experiencing the events. This is taken as indicating
that the mouse is recalling the event. A startling event is indeed
something to be remembered.
While the “bubbles” that result from the data analysis show
distinct patterns for rest and the events, a more interesting thing
to me was the finding that the neurons form what Tsien calls
“neural cliques”. The researchers found that certain sets of
neurons respond to particular characteristics. Tsien concludes
that some neurons respond to the general category of a “startling
event”, an event that’s unexpected and sufficiently unnerving to
warrant filing it for future reference. Another clique responds to
a “disturbing motion”; this clique of neurons would respond to
the shaking and dropping but not to an air puff. Other cliques
respond to the more specific motions of shaking and of dropping
and to an air puff.
Tsien likens the building of a memory to a pyramid. Take, for
example, the shaking. The base of the pyramid is the general
feature (here the startling event). Building on the base is the
more specific disturbing motion. On top of that is the more
specific type of motion - shaking. On top of that, at the peak of
the pyramid, there might be a clique that responds to location of
the shaking, which for the mouse might be in a black box. Each
memory is wired into the brain by the firing of the cliques
associated with the various features of the event. This pyramid
with a very general property at the base and becoming more and
more specific as the pyramid builds to its peak is a useful
concept to represent how a memory is built.
Obviously, Tsien and his team have only monitored a small
number of neurons out of immense numbers in the brain, even of
a mouse. There probably are other cliques that fill in other
features of the startling events such as the intensity of the
shaking. The number of neurons in the cliques is also up in the
air. Tsien cites the work of Itzhak Fried of UCLA. Fried was
studying neurons in the hippocampus of epilepsy patients and
found that in one patient a particular neuron fired only in
response to actress Halle Berry. We know celebrities have their
groupies. Tsien suggests Halle may have a clique of neurons!
Tsien carries the concept even further by asking if the memory
can be digitized. That is, can it be converted to the 1’s and 0’s of
the typical computer code? Let’s digitize our mini earthquake.
It is a startling event (1), a disturbing motion (1), not a drop or
free fall (0), not an air puff (0) but is a shaking (1). The digital
code for our mini earthquake would therefore be 11001. Tsien
and his group have digitized their results from four different
mice and can with almost 100% accuracy predict the event a
mouse has experienced and its location from the digital code they
derive from their data on the firing of the cliques of neurons.
Tsien’s final statement in the article is truly scary. If memory
can be digitized, Tsien speculates that perhaps 5,000 years from
now we might be able to download the contents of our minds
onto computers and live forever on the network! Tennessee
Williams probably never considered that type of life as a
possibility! That’s more an Orwell kind of thing.
Allen F. Bortrum
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