Preface_2003_Mechanisms-of-Memory

Prévia do material em texto

This book is primarily intended for
advanced undergraduates, graduate stu-
dents, and researchers interested in learn-
ing and memory. After a brief introduction
to the basics of learning and memory at the
psychological level, the book will describe
current understanding of memory at the
molecular and cellular level. Particular
emphasis will be on the hippocampus and
its role in declarative and spatial learning,
although examples from other anatomical
and behavioral systems will also be used.
As the book overall progresses from chapter
to chapter, I will deliberately move from
well-established facts and background, to a
description of current work and thinking in
the area, to at last what should be clearly
labeled speculation.
In my opinion, this book is appropriate
for use in advanced undergraduate and
graduate-level learning and memory
courses, courses that typically are based in
Psychology, Biology, and Neuroscience
Departments at the University and Medical
School levels. I hope that it provides a
nice foundation for thinking about
the molecular underpinnings of synap-
tic plasticity and information storage.
However, the book is primarily targeted
to active researchers (at all stages of
their career development) in the learning
and memory fields.
One goal of the book is to begin to
embrace the complexity of mechanisms of
learning and memory at the molecular
level. Some who work on the cellular
processes of learning and memory seem to
want to ignore this complexity, deny its
existence, or throw up their hands in
frustration and imply that the problem is
insoluble. I share none of these viewpoints.
My hope in this book is to begin to organize
a framework of thinking about synaptic
plasticity and memory at the molecular
level—one which recognizes and begins to
incorporate this extreme biochemical com-
plexity into our thinking about memory. I
note that building these models is at a
relatively early stage, but one thing the
reader hopefully will take from the book is
some perspective on where we stand at
present and where the future may lie.
Most of us have seen the large and
complex schematic diagrams summarizing
intermediary metabolism. Hundreds of
discrete and highly regulated enzymatic
steps are necessary for the relatively basic
function of converting glucose into ATP.
How can memory be any less complex than
that at the molecular level? Human
learning and memory is likely the most
highly evolved and sophisticated biologi-
cal process in existence. In my view,
the ultimate molecular understanding of
xiii
Preface
8957-Prelims 25/7/03 11:56 AM Page xiii
learning and memory will make processes
such as intermediary metabolism seem
simple in comparison. This book represents
one first step at beginning to put together
the complex puzzle of the molecular basis
of memory.
While a strong case can be made that the
molecular basis of memory will of necessity
be quite complex at the biochemical level,
a more difficult argument arises as to
whether understanding these processes is
even really important. Is it molecular stamp
collecting? If all the nervous system really
cares about is the firing of action potentials,
isn’t the underlying biochemistry really just
housekeeping? A second point that I want
to try to make with this book is that
understanding the underlying molecular
basis is important. Where possible, I will try
to utilize examples illustrating that various
molecular processes are being used for
information processing; information process-
ing that occurs at a level independent of
patterns of action potential firing. Also, I
want to highlight that action potentials and
neurons per se are incapable of storing
information. That is because all biological
processes are subserved by biochemical
phenomena. This book is written from the
perspective that, in the limit, neurons are
bags of chemicals and the fundamental unit
of information storage is the molecule.
This book seeks to take the reader from a
basic background of learning theory and
synaptic physiology, to a detailed discus-
sion of the biochemical mechanisms of
long-term changes in synaptic function and
information storage, to a discussion of the
molecular basis of learning and memory
disorders. Themes that are highlighted
include:
• Genes and gene regulation in memory
formation.
• The role of long-term changes in
synaptic function in memory.
• Does Long Term Potentiation =
Memory?
• Multimodal signal integration at the
molecular level and its role in cognition
as related to memory.
• Learning disorders with a focus on
mental retardation syndromes.
• Memory disorders with a focus on
Alzheimer’s Disease.
• The biochemical basis of cellular
information processing.
• Biochemical mechanisms for
information storage.
A few comments concerning references
are in order. There have been many
thousands of publications in the fields that
are covered by this book. The chapters
covering LTP biochemistry, which is the
area that the book covers in the greatest
detail, are drawn from about 900 primary
publications. Some single paragraphs in
these sections summarize work from about
50 different research papers. In writing the
book, I had to make a decision – I could
write sentences like “Postsynaptic calcium
is known to be involved in LTP induction:
blocking a rise in postsynaptic calcium
blocks LTP induction, elevating post-
synaptic calcium elicits synaptic poten-
tiation, and a rise in postsynaptic calcium
has been shown to occur with LTP-
inducing stimulation.” Or I could write
sentences like “X et al., Y et al., and Z et al.
showed that injecting calcium chelators
postsynaptically blocked LTP induction,
P et al., Q et al., and Z et al. showed that ….”
The latter type of sentence, the historical
narrative, obviously has a more scholarly
tone and gives appropriate credit to X et al.,
etc. However, it rapidly leads to bloated
verbiage that is much more difficult to read.
Taking all this into consideration, I decided
to handle the citations in the following way.
At the end of each chapter is a section titled
“References,” which is a little different from
the typical list of references in terms of its
content. It is not exhaustive. “References” is
the short list of papers that were the
xiv PREFACE
8957-Prelims 25/7/03 11:56 AM Page xiv
principal papers I used in preparing the
chapter, and there is a distinct bias toward
citing reviews that I feel are particularly
lucid and informative. In a real sense, the
references are my list of recommended
readings for further information. The cited
reviews are a place where readers looking
for more detailed references can find cita-
tions to the extensive list of primary litera-
ture. I apologize in advance to the many
researchers whose primary papers I have
not cited directly. 
I strongly encourage anyone with any
complaint, correction, criticism or sug-
gested addition to e-mail me (david@cns.
neusc.bcm.tmc.edu). Constructive criticism
is the only means by which the content of
the book may be improved in the future. So,
when John Lisman wants to fire off a
scathing critique of my inadequate repre-
sentation of his work, I encourage him to
send me an e-mail so that I can take his
comments into consideration in future
writing efforts. I want to emphasize that I
encourage everyone to do this. I want the
post-doc who spent two years optimizing
assays for measuring protein kinase
activation, so that they could measure an
LTP-associated increase in CaMKII, to be
able to e-mail me and get at least some
recognition for their effort. In cases like this
it is likely to be helpful to send me the
relevant citation and a few sentences
describing its significance and relevance.
The overall goal of encouraging this sort of
interaction is to allow a means for
dynamically correcting and updating the
book content.
Finally, I am more than happy to share
Powerpoint files containing the figures
from the book with anyone who would like
to use them for teaching purposes, etc. An
e-mail to the above addresswill suffice to
get that particular ball rolling.
David Sweatt
xvPREFACE
8957-Prelims 25/7/03 11:56 AM Page xv