Medical neurobiology

682 Pages·2011·16.429 MB·English

by  Peggy Mason PhD

Medical Neurobiology
The following people kindly reviewed early manuscript pages of M edical Neurobiology and provided useful comments:
A. Cyrus Arman Ivan Kirov
Aida Attar Nicholas Kroll
Annamaria Barczak Crystal Miller
Blaire Beers-Mulroy Josh Neman
Alex Brownell Tanvi Patel
Tina Burton Katherine Poruk
Sarah Busch Serendipity Zapanta Rinonos
Jennifer Choi Nicole Sabaliauskas
Erika Chung Sruthi Swaminathan
Yi Dong Matt Vestal
Thomas Engar Guangying Wu
Stephanie Fox Synphen Wu
Elan Grossman Letisha Wyatt
Brad Heller Ghiam Yamin
David Herman Jing Yang
April Ho Elizabeth A. Young
Carrie Johnson
Medical
Neurobiology
Peggy Mason, PhD
Department of Neurobiology
The University of Chicago
Chicago, IL
1
1
Oxford University Press, Inc., publishes works that further
Oxford University’s objective of excellence
in research, scholarship, and education.
Oxford New York
Auckland Cape Town Dar es Salaam Hong Kong Karachi
Kuala Lumpur Madrid Melbourne Mexico City Nairobi
New Delhi Shanghai Taipei Toronto
With offi ces in
Argentina Austria Brazil Chile Czech Republic France Greece
Guatemala Hungary Italy Japan Poland Portugal Singapore
South Korea Switzerland Thailand Turkey Ukraine Vietnam
Copyright © 2011 by Oxford University Press, Inc.
Published by Oxford University Press, Inc.
198 Madison Avenue, New York, New York 10016
www.oup.com
Oxford is a registered trademark of Oxford University Press
All rights reserved. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording, or otherwise,
without the prior permission of Oxford University Press.
Library of Congress Cataloging-in-Publication Data
Mason, Peggy, Ph.D.
Medical neurobiology / Peggy Mason.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-19-533997-0 (alk. paper)
1. Neurobiology. I. Title.
[DNLM: 1. Nervous System Physiological Phenomena. 2. Nervous System Diseases. WL 102]
QP355.2.M37 2011
612.8—dc22
2010034433
9 8 7 6 5 4 3 2 1
Printed on acid-free paper
Over the years of this project, I often wondered why I chose to take on
this task. In the end, I came to the realization that I wrote this book for
the same reason that I teach neurobiology: to communicate the beauty,
intricacy, and everyday importance of the nervous system.
This page intentionally left blank
Pr eface
A
t the start of the 20th century, medical education in North America
was almost universally substandard with few or no requirements for
admission, graduation, or competency. In 1905, the American Medical
Association boldly recommended broad changes including admis-
sion requirements, as well as an initial 2-year curriculum in basic science. 1 Over the
ensuing decade, these recommendations were implemented in American and
Canadian medical schools and have continued, with some modifi cations, to the
current time. Currently, a full year of basic science by basic scientists is taught at
most North American medical schools. A minority of the basic scientists who teach
these courses have a medical degree, and an even smaller proportion are practicing
clinicians. As a result, a tension has built up between the basic interests and abilities
of the scientist teachers and the clinical interests and goals of the students desirous
to be physicians. Basic scientists teach what is important to them more than what is
clinically relevant, assuming that the medical students will receive clinical training in
future courses on pathophysiology taught by clinicians. The medical students feel as
though they are being asked to learn material that has varied relevance to their future
profession. The fact that the goals of students and teachers diff er hinders communi-
cation and frustrates both students and teachers. The innocent bystander hurt by this
problem is the subject itself, the beautiful world of neurobiology.
I taught in the fi rst-year medical neurobiology course at the University of
Chicago for 15 years and directed this course for 7 years, encountering directly the
tension between basic science and medicine. Throughout most of my participation
in medical neurobiology, I taught what I considered fundamental neurobiological
principles, along with the occasional clinical anecdote thrown in to pique the stu-
dent’s interest. A few years ago, however, I had the opportunity and pleasure of
talking in depth with four medical students 2 —Markus Boos, Eileen Rhee, Vance
Broach, and Jasmine Lew. The conversation occasioned an epiphany from which this
book was born. My epiphany centered on (1) the volume of information that medical
students must master in 2 years, from gross anatomy and histology to physiology,
microbiology, and neurobiology; and (2) the impressive sincerity of medical students’
desires to be great physicians and to help people.3 Understanding medical students’
1 Council on Medical Education of the American Medical Association, JAMA 44:1470–75,
1905.
2 At the time, all were students and now all are either residents or physicians.
3 It is my impression that the vast majority of medical students are motivated by some
degree of altruism. In contrast, students pursue a Ph.D. degree in science for a number of
reasons including the intellectual thrill, curiosity, the fun of laboratory work, and also in some,
but certainly not all, cases the desire to improve human health. The often dichotomous motiva-
tions of basic scientists and physicians are another source of potential misunderstanding.
vii
sincere altruism led to my recognition that any resistance that I perceived on the part
of the students to learning course material was not attributable to disinterest or lack
of motivation. Rather, students were making a realistic assessment of how to go from
college-level biology to practicing medicine in 4 short years and were allotting their
time and energy accordingly.
With my newfound insight, I looked anew at the material that we taught in med-
ical neurobiology. I realized that a more comfortable union between basic science and
clinical interests could and indeed s hould be forged. I now believe that what students
deserve from a fi rst-year, basic science neurobiology course is a logical framework
that allows them to understand how the nervous system infl uences the breadth of
human biology. An introductory course in neurobiology for medical students should
not be designed to teach neurology. Rather, the goal should be to communicate the
relevance of the nervous system to the practice of e very medical specialty from car-
diology to dermatology, neonatology, pediatrics, geriatrics, pulmonology, ophthal-
mology, and so on.
A single book in a single voice that teaches fundamental neurobiological
concepts important to clinical practice was my objective in writing this textbook.
Because this book is aimed more at the future internist than the future neurologist,
no topic is covered in an encyclopedic fashion and thus this book is n ot a reference
book. There are many outstanding reference books on topics related to the nervous
system. Many of these were invaluable to me as I prepared this book. There are
a number of excellent texts on neuroanatomy, neurology, and neuroscience that
I encourage those of you whose interest is piqued to explore further.
Medical Neurobiology is intended to teach, explain, and clarify neurobiological
concepts that will impact your lives as physicians. Essentially, your understanding is
the ultimate test of the success of this book. Therefore, I am interested in your reac-
tions, and I encourage you to send feedback to [email protected].
No author is an island, and I certainly have benefi ted from the generosity and
insight provided by countless individuals. In particular, I thank the hundreds of med-
ical and graduate students whom I have taught over the years. Questions like “How
do we sense wet?” have permitted me to see neurobiology afresh and also pushed me
to learn new pieces of neurobiology. I feel particularly grateful to the Pritzker class
of 2009 who, as my post-epiphany guinea pigs, worked with me to hone my ideas
for how medical neurobiology should be taught. These students worked hard, they
engaged the brain, struggled with the material, and most importantly, respected the
brain—all that this basic scientist could ever ask for. My hope for this book is that
it will catalyze more and more medical students to fully engage and appreciate the
wonders of the nervous system.
viii Preface
Ack nowledgments
I
thank Madelyn Baez, Thaddeus Brink, Howard Fields, Aaron Fox, Jay
Goldberg, Elizabeth Grove, Kevin Hellman, Gert Holstege, Un Jung Kang, Don
Katz, Philip Lloyd, Bob McCrea, Scott Mendelson, Kathy Millen, Malcolm
Nason, Bob Perlman, Don Pfaff , Cliff Ragsdale, Peter Redgrave, Clif Saper,
and Murray Sherman for their willingness to discuss and debate the mysteries of
neural function and structure over the years. For generously and patiently responding
to my questions, I am indebted to Ben Barres, Jack Feldman, Stanford Gregory, Jon
Levine, Courtenay Norbury, Sam Sisodia, and Ruediger Thalmann. Cate Kiefe and
Klara Scharnargl helped with illustrations. Jonathan Barnett, Andrew Bell, Adrian
Danek, John Dowling, Andrew Engel, Patrick Hof, Anna Lysakowski, Jane Mason,
Claude Perreault, Gisèle Perreault, and Caitlin Trasande were kind enough to share
images with me, and I thank them. Larry Wood, Holly Humphrey, Scott Stern, and
Halina Bruckner helped me fi nd the common ground between basic science and
medicine. Bob Burke, Lynette Daws, Elizabeth Grove, Kevin Hellman, Philip Lloyd,
Bob Perlman, Peter Redgrave, Murray Sherman, Steve Shevell, Sarah Sweitzer,
Tom Thach and Steve Waxman were kind enough to go over chapters, in some cases
repeatedly. I am grateful to the University of Chicago and to my chairman, Murray
Sherman, for support and encouragement throughout the years of this project.
A few people deserve special mention for help above and beyond either my expec-
tations or my due. Philip Lloyd patiently read and commented on chapters on neural
signaling over and over again, as well as on many additional chapters. His comments
were always an entertaining blend of scientifi c rigor and wry humor. Philip saved
me from numerous sloppy blunders, and I am more grateful than a forever supply
of heirloom tomatoes can express. Bob Perlman has been an invaluable friend and
source of encouragement. I have run to Bob repeatedly to understand the infl uence of
evolution on our bodies and brains. Bob never disappoints. Bob possesses a unique
blend of thoughtfulness, logical clarity, and compassion that I treasure. My friend and
colleague, Kevin Hellman, has generously accompanied me on this journey, reading
and commenting on e very chapter . His humor, broad knowledge and interest in sci-
ence, and positive attitude have buoyed my spirits time after time. Most importantly,
the love for the brain implicit in Kevin’s comments and suggestions has enriched this
book immeasurably. Despite all of the help from my wonderful colleagues, mistakes
remain. These mistakes are entirely due to my own shortcomings and stubbornness.
Craig Panner, my editor at Oxford University Press, believed in this project long
before it was deserving of his faith. I remain both perplexed and deeply appreciative
for his nearly immediate confi dence in me and the project. Craig’s calm served as the
perfect antidote to this fi rst-time author’s occasional panic, and I am indebted to him
for that. David D’Addona, also of Oxford University Press, was supportive, effi cient,
ix