Table Of ContentGROWTH OF THE NERVOUS SYSTEM
GROWTH OF THE
NERVOUS SYSTEM
A Ciba Foundation Symposium
Edited by
G. E. W. WOLSTENHOLME
and
MAEVE O’CONNOR
LITTLE, BROWN AND COMPANY
BOSTON
First published 1968
With 101 illustrations
Standard Book Number 7000 I353 9
ALL RIGHTS RESERVED
This book is protected under the Berne Convention. It may not be reproduced by any
means, in whole or in part, without permission. Application with regard to reproduction
should be addressed to the Publishers.
Printed in Great Britain
Contents
Sir John Eccles Chairman’s opening remarks I
Session I Development of specific neuronal connexions
J. Szentfigothai Growth of the nervoussystem: an introductorysurvey 3
S. M. Crain Formation of functional interneuronal connexions
E. R. Peterson between explants of various mammalian central
M. B. Bornstein nervous tissues during development in vitro 13
Discussion Crain, Eccles. Gaze, Hnik, Kerkut, Murray, Sperry,
Stefanelli, SzCkely 31
R. W. Sperry Regulative factors in the orderly growth of retino-
E. Hibbard tectal connexions 41
R. M. Gaze Cell division and migration in the brain after optic
W. E. Watson nerve lesions 53
Discussion Buller, Drachmon, Eccles, Gaze, Hamburger, Hughes,
Kollros, Levi-Montolcini, Prestige, Singer, Sperry,
SzCkely, Szentcigothai, Walton, Young 67
G. SzCkely Development of limb movements: embryological,
physiological and model studies 77
Discussion Drochman, Eccles, Gutmann, Hnik, Hughes, Kerkut,
Kollros, Piatt, SzCkely 93
General Discussion Eccles, Hamburger. Hughes, Sperry, SzCkely, Szentdgothoi 96
Session 2 Development of movement
V. Hamburger The beginnings of coordinated movements in the chick
embryo 99
Discussion Buller, Drachman, Eccles, Hamburger, Hnik, Hughes,
Kerkut, Kollros, Levi-Montolcini, Mugnaini, Muntz,
SzCkely, Szentdgothoi, Walton I05
A. Hughes Development of limb innervation I10
Discussion Drochmon, Eccles, Gaze, Gutmonn, Hamburger, Hnik,
Hughes, Kerkut, Kollros, Levi-Montalcini, Piott, Prestige,
Singer, SzCkely, Szentcigothoi, Walton I I7
Session 3 Role of chemically specific signals in the development of
the nervous system
Rita Levi-Montalcini Biological aspects of the nerve growth factor I26
P. U. Angeletti
Discussion Croin, Drochman, Eayrs, Eccles, Gutmonn, Kerkut, Levi-
Montalcini, Murray. Singer, Szentcigothai I 42
V
vi CONTENTS
Margaret R. Murray Action of heavy water [D20] on growth and develop-
Helena H. Benitez ment of isolated nervous tissues I4 8
Discussion Crain, Gaze, Hnik, Kerkut, Levi-Montalcini, Muntz,
Murray, Szentdgothai I74
J. J. Kollros Endocrine influences in neural development I79
Discussion Crain, Eayrs, Hughes, Kerkut, Kollros, Levi-Montalcini,
Piatt, Prestige, Stefanelli, SzCkely, Szentdgothai I92
Session 4 Trophic interaction, peripheral and central
M. Singer Penetration of labelled amino acids into the peripheral
nerve fibre from surrounding body fluids 200
Discussion Drachman, Eccles, Gaze, Hughes, Mugnaini, Murray,
Singer, Stefanelli, Szentdgothai, Walton, Young 21 5
G. A. Kerkut Transport of material along nerves 220
Discussion Buller, Crain, Drachman, Eccles, Gaze, Gutmann, Hnik,
Hughes, Kerkut, Mugnaini, Szentdgothai, Young 229
E. Gutmann Development and maintenance of neurotrophic
relations between nerve and muscle 233
Discussion Buller, Drachman, Eccles, Gutmann, Hnik, Hughes,
Kerkut, Levi-Montalcini, Murray, Prestige, Szentdgothai,
Walton, Young 243
D. B. Drachman The role of acetylcholine as a trophic neuromuscular
transmitter 25 I
Discussion Crain, Drachman, Eccles, Gutmann, Hnik, Kerkut, Singer,
SzCkely, Walton, Whittaker 273
General Discussion Eccles, Gutmann, Hamburger, Hughes, Kollros, Mugnaini,
Prestige, Stefanelli, Szentdgothai, Walton 279
Author index 289
Subject index 290
Membership
Symposium on Growth ofthe Nervous System held 21st-23rd June, 1967
Sir John Eccles Institute for Biomedical Research, Chicago, Illinois
(Chairman)
A. J. Buller Department of Physiology, The Medical School, University
of Bristol
S. M. Crain Department of Physiology, Albert Einstein College of
Medicine, Yeshiva University, New York
D. B. Drachman New England Medical Center Hospitals, Boston, Massa-
chusetts
J. T. Eayrs Department of Neuroendocrinology, Institute of Psychiatry,
The Maudsley Hospital, London
R. M. Gaze Department of Physiology, University Medical School,
Ed inb u rgh
E. Gutmann Czechoslovak Academy of Sciences, Institute of Physiology,
Prague
V. Hamburger Department of Biology, Washington University, St. Louis,
Missouri
P. Hnik Czechoslovak Academy of Sciences, Institute of Physiology,
Prague
t
A. Hughes Department of Zoology, University of Bristol
G. A. Kerkut Department of Physiology and Biochemistry, University of
Southampton
J. J. Kollros Department of Zoology, University of Iowa, Iowa City, Iowa
Rita Department of Biology, Washington University, St. Louis,
Levi-Montalcini Missouri
E. Mugnaini Anatomisk Institutt, Universitetet i Oslo, Norway
Louise Muntz Department of Zoology, University of Bristol
f Present address: Department of Anatomy, Western Reserve University School
of Medicine, Cleveland, Ohio.
vii
viii MEMBERSHIP
Margaret R. Murray Department of Surgery, College of Physicians and Surgeons,
Columbia University, New York
J. Piatt Department of Anatomy, The School of Medicine, University
of Pennsylvania, Philadelphia, Pennsylvania
M. C. Prestige Department of Zoology, University of Bristol.
M. Singer Department of Anatomy, Western Reserve University
School of Medicine, Cleveland, Ohio
R. W. Sperry Division of Biology, California Institute of Technology,
Pasadena, California
A. Stefanelli lstituto di Anatomia Comparata “Battista Grassi”, Univer-
sit& di Roma, Rome
G. Szbkely Department of Anatomy, University Medical School, PCcs,
Hungary
J. Szentgothai Department of Anatomy, University Medical School,
Budapest, Hungary
J. N. Walton Regional Neurological Centre, Newcastle General Hospital,
Newcastle upon Tyne
V. P. Whittaker Department of Biochemistry, University of Cambridge
1. Z. Young Department of Anatomy, University College London
The Ciba Foundation
The Ciba Foundation was opened in 1949 to promote
international cooperation in medical and chemical
research. It owes its existence to the generosity of CIBA
Ltd, Basle, who, recognizing the obstacles to scientific
communication created by war, man’s natural secretiveness,
disciplinary divisions, academic prejudices, separation by distance
and by differences in language, decided to set up a philanthropic
institution whose aim would be to overcome such barriers.
London was chosen as its site for reasons dictated by the special
advantages of English charitable trust law (ensuring the indepen-
dence of its actions), as well as those of language and geography.
The Foundation’s house at 41 Portland Place, London, has
become well known to workers in many fields of science. Every
year the Foundation organizes six to ten three-day symposia
and three or four shorter study groups, all of which are published
in book form. Many other scientific meetings are held, organ-
ized either by the Foundation or by other groups in need of a
meeting place. Accommodation is also provided for scientists
visiting London, whether or not they are attending a meeting
in the house.
The Foundation’s many activities are controlled by a small
group of distinguished trustees. Within the general framework
of biological science, interpreted in its broadest sense, these
activities are well summed up by the motto of the Ciba Foun-
dation : Consocient Gentes-let the peoples come together.
ix
I*
Preface
DR. ARTHURH UGHEfiSrs t suggested that the Growth of the
Nervous System would be an appropriate subject for a Ciba
Foundation symposium. It seemed a good time for those who were
studying the development of the nervous system and its connexions
in the non-human maturing embryo to share their thoughts with
scientists working on the transmission of impulses along the nerve
fibres to and from specific end-organs in man and other adult
animals. Another aim of the meeting was to try to link this basic
material with the ways in which the development of the central
nervous and neuromuscular systems could go wrong in man.
After many pleasant discussions with Arthur Hughes (by letter
and in person) and Sir John Eccles (by letter), the meeting took
shape.
SirJ ohn was our chairman. This is the second occasion on which
he has taken the chair at a Ciba Foundation symposium, and once
again his scientific curiosity and his dedication to the nervous
system ensured that he performed this function most ably. He was
as always a tremendous stimulus to all the members.
We were particularly privileged that Lord Adrian came to some
of the sessions. As well as his perpetual interest in and contri-
butions to the physiology of the nervous system he has been (and
still is) mentor to several of the members of the symposium.
We would especially like to thank Arthur Hughes for his help
in editing these proceedings, and for his non-stop enthusiasm
before, during and after the meeting.
We hope that the questions uncovered and unanswered at
the symposium and set down in this volume may-perhaps
because of their number and complexity-be a challenge to all
workers in this field.
xi
GROWTH OF THE NERVOUS SYSTEM
Edited by G. E. W. WOLSTENHOLME and MAEVE 0 'CONNOR
Copyright 0 Ciba Foundation
CHAIRMAN'S OPENING REMARKS
SIR JOHN ECCLES
I am very honoured to be again the Chairman of a Ciba Foundation
symposium. The last symposium I chaired here was on the nature of sleep.
My problem was of course to prevent participants from giving practical
demonstrations ! In fact this is the fifth Ciba Foundation conference I have
attended, and I can assure those of you who have not been here before that
they are most delightful and instructive, friendly and sociable occasions.
I am glad to welcome Lord Adrian here today. He has experienced
personally the whole development of investigations on the nervous system
at a tremendously exciting period. I want also to thank Dr. Hughes and to
say how much I admire the way in which he has developed this conference
and helped to choose the various participants.
Now I want to say a few words about the subject of our symposium.
You will appreciate that I am quite obsessional about the nervous system
and therefore you may discount quite a lot of what I tell you. Maybe you
are obsessional too-I hope that you are. First, the fully developed brain,
such as mammals possess, is the most complex organization of matter
known to occur. The second remarkable thing is that it has just grown. It
is not even organized by activity. We know, for example, from Hubel and
Wiesel's work that the specific connexions from the retina to the occipital
cortex are there before the kitten has opened its eyes and before there has
been any retinal stimulation. This extreme complexity has grown without
the help of any outside signals and even without any activity of a nervous
system playing some role in the neurogenesis. Undoubtedly activity does
modulate the later more subtle changes that take place, including the plastic
changes in memory, but before that ever starts at all this extremely complex
organization of the brain is already in existence.
To study the growth ofthe brain as such would be an almost insuperable
task and most of this conference will be about the simpler aspects of growth
and organization such as can be seen, for example, in the peripheral nervous
system, or in the simpler animals under controlled conditions. But all of it
hangs together in giving us insight until eventually we shall be able to
understand how a nervous system is put together or grows. This conference
is on the scientific efforts we have made on this seemingly impossible
problem. But we can make progress, and a conference like this is a witness
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