Name: How Memory Works
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<div class="rich-text">(Program not available for streaming.) What are memories? How do they form, and why do they seem so real? How could a famous psychology subject named H.M. retain long-term memories of his childhood yet not recall short-term memories, like what he ate for lunch? Neurobiologists and psychologists are discovering the details of how memory works, including pinpointing molecules that can create memories as well as those that can erase memories forever.
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Neurobiologists are honing in on how memories form, and then finding ways to erase them.

The Brain Observatory, University of California, San Diego

Brain & Cognitive Sciences, Massachusetts Institute of Technology

New York University

Columbia University

McGill University

<div class="rich-text">Neurobiologists are honing in on how memories form, and then finding ways to erase them.</div>

How Memory Works

Body & Brain

<div class="rich-text"><h3>
 How Memory Works
</h3>

 PBS Airdate: August 25, 2009



 NEIL
DeGRASSE TYSON:
 
 Most of us hold in
our minds, memories of our lives, so vivid that when we recall them, they seem
real and indelible. They're an essential part of who we are. But as we explore
the mechanics of the brain, we're starting to learn exactly what these memories
are made of. And it turns out a lot of it boils down to chemistry.


 As
correspondent Chad Cohen reports, researchers are discovering the precise
molecules that can create memories, as well as the molecules that can erase
them forever.



 CHAD
COHEN
 
 (Correspondent): This is the brain that, more than any other in
history, has allowed scientists to make sense of your brain. For 82 years, it
resided in the head of a man named Henry Gustav Molaison, better known as H.M.
He was, perhaps, the most-studied patient ever. And that didn't end when he
died last year.


 With
H.M.'s permission, neuroanatomist Jacopo Annese went to work, dissecting his
brain into 3,000 slices.



 JACOPO
ANNESE
 
 (The Brain Observatory/University
of California, San Diego): You can imagine the brain being like a book, and our
tissue slices are the pages of this book. The only catch is that the slices are
transparent. So you cannot really see anything until you use a lot of obscure
chemical processes to reveal the features in the tissue. Eventually, the entire
book will be completely stained. And they will tell us the story of this brain.



 CHAD
COHEN:
 
 It's a story that begins with epilepsy, epilepsy
so severe that by 1953, H.M. had reached his breaking point.



 SUZANNE
CORKIN
 
 (Massachusetts Institute of Technology): He had to stop working because of the frequency of
his seizures. It was just too dangerous. So he was basically at home with his
parents. His life was on hold.



 CHAD
COHEN:
 
 In desperation, H.M. let surgeon William Scoville
remove slivers of brain on either side of his head, each containing a
seahorse-shaped structure called a hippocampus. This might have seemed
reasonable at a time when we knew almost nothing about memory. And it did quiet
his seizures, though at a terrible cost.



 SUZANNE
CORKIN:
 
 Do you know what you did
yesterday?



 HENRY
GUSTAV MOLAISON
 
 (Epilepsly Patient/File
Footage): No, I don't.



 SUZANNE
CORKIN:
 
 How about this morning?



 HENRY
MOLAISON:
 
 That, I don't know myself. I can't
tell you because I don't remember.



 CHAD
COHEN:
 
 H.M.'s condition might have seemed like simple
dementia, but as neuroscientist Brenda Milner discovered, it was anything but.



 BRENDA
MILNER
 
 (Montreal Neurological Institute): He would say, "Right now it's like waking from a
dream. Right now everything is clear. But what happened just before?"



 CHAD
COHEN:
 
 Milner found that H.M. had a normal I.Q. He could
crack jokes, solve puzzles. Even, to some extent, remember.



 ERIC
KANDEL
 
 (Columbia University): So H.M. could remember everything that happened
prior to the operation. He could remember the trauma of his childhood. He could
remember going to elementary school, to high school, working in the assembly
plant.



 CHAD
COHEN:
 
 What he couldn't do was hold on to new
information for more than a few minutes. In a moment of insight, Milner
concluded the hippocampus must make long-term memories out of short-term ones.



 SUZANNE
CORKIN:
 
 That was a groundbreaking finding
because it showed that the ability to establish long-term memories is localized
to this tiny area in the brain.



 CHAD
COHEN:
 
 If H.M. had contributed nothing more, his fame
would have been assured. But he would go on inspiring discoveries for decades.
The next involved a pencil, a mirror and, again, Brenda Milner.



 ERIC
KANDEL:
 
 She did this brilliant test in which she had H.M.
draw the outlines of a star without looking at the star, but looking into a
mirror.



 CHAD
COHEN:
 
 It's hard, at first, to draw within the lines,
but could H.M., like people with normal memory, learn to do it with practice?


 After
three days and 10 trials, his performance was nearly perfect.



 BRENDA
MILNER:
 
 Well, he said, "I thought this
would be difficult, but it looks as though I've done pretty well." He had no
memory of all these learning trials that he had been through, and the beautiful
learning, that was the real contrast.



 CHAD
COHEN:
 
 So H.M. could remember a motor skill, but not
recall a fact or an event. It was a key discovery, because it showed there were
different kinds of memory, dependant on different parts of the brain.


 But
what is a memory, anyway?


 Nerve
cells communicate by sending electrical signals, which trigger the release of
chemicals across tiny gaps called synapses. As one cell speaks to another,
chemical changes at the synapse make it easier for the signals to pass. If only
a few signals are sent, this transformation among a network of cells is
temporary, resulting in a short-term memory. But if the signals keep coming,
changes at the most active synapses become permanent, forming a long-term
memory.



 ERIC
KANDEL:
 
 So long-term memory actually involves an anatomical
change in the brain. So, as I like to say, if you remember anything about this
conversation tomorrow, it's because you will have a slightly different head
than you had today.



 CHAD
COHEN:
 
 But what maintains a long-term memory? How can
you recall something that you may not have thought about for 20 years?


 Neuroscientists
Todd Sacktor and Andre Fenton think the answer may lie in a molecule called
PKMzeta that accumulates at synapses as memories form.



 ANDRE
FENTON
 
 (SUNY, Downstate Medical Center): PKMzeta acts as glue, if you will, for fixing the
connections amongst the neurons that were active together. So that later in
time, those neurons are bound together and permanently bound together, and can
become active again to recall the experience.



 CHAD
COHEN:
 
 To assess the molecule's importance, Fenton set
up an experiment that would give the rat a memory. He placed it on a revolving
table, where in one area it would receive a mild shock.



 ANDRE
FENTON:
 
 There's the rat, and he's approaching the shock zone. He's beginning to
move a little bit but looks like he's going to enter the shock zone. He's
gotten shocked, and he's just run away. He's approaching it right now.



 CHAD
COHEN:
 
 Soon, the rat always avoided the shock zone.



 ANDRE
FENTON:
 
 So when the rat stays away from a particular area, we can imagine that
he has remembered where he was shocked.



 CHAD
COHEN:
 
 Then Fenton injects the rat's hippocampus with a
chemical called ZIP, known to undo the effect of PKMzeta.



 ANDRE
FENTON:
 
 And what we observed, which was quite remarkable, was the rat acted as
though it had forgotten completely where the shock zone was. And it explored
the arena as if it was in the arena for the first time.


 Just
got shocked.



 CHAD
COHEN:
 
 Yet the rat could learn once again to avoid the
shock zone.



 ANDRE
FENTON:
 
 So we hadn't damaged the rat's brain. We hadn't broken its ability to
learn anything. What we had simply done was specifically erased the memory for
that shock zone.



 CHAD
COHEN:
 
 Without PKMzeta, the rat cannot maintain a
long-term memory. While this is not the only molecule active at synapses, it
does appear we may have found a crucial ingredient of memory, one that explains
how a three-pound lump of flesh can store, indefinitely, vivid recollections of
everything from birthdays to weddings, to episodes of NOVA scienceNOW.


 Meanwhile,
the man who launched the modern era of brain research is making his final
contribution. Three thousand glass slides of H.M.'s brain are being posted on
the Internet, where researchers will be able to examine them down to the level
of individual neurons.


 And
what would H.M. have thought about all this?



 HENRY
MOLAISON:
 
 The way I figure it is what they
find out about me helps them to help other people.


 On
Screen Text: We asked scientists to critique our depictions of
neurons.


 1. The synapse: a neural junction used for communication between neurons.


 Too
far apart.


 Closer.


 Even
closer.


 Alright.


 Also...


 2. Why all the flashing lights? Electricity doesn't zap through your house like this. And it doesn't in your brain, either. Good thing.
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