ADVANCES IN PHYSIOLOGICAL SCIENCES Proceedings of the 28th International Congress of Physiological Sciences Budapest 1980 Volumes 1 - Regulatory Functions of the CNS. Principles of Motion and Organization 2 - Regulatory Functions of the CNS. Subsystems 3 - Physiology of Non-excitable Cells 4 - Physiology of Excitable Membranes 5 - Molecular and Cellular Aspects of Muscle Function 6 - Genetics, Structure and Function of Blood Cells 7 - Cardiovascular Physiology. Microcirculation and Capillary Exchange 8 - Cardiovascular Physiology. Heart, Peripheral Circulation and Methodology 9 - Cardiovascular Physiology. Neural Control Mechanisms 10 - Respiration 11 - Kidney and Body Fluids 12 - Nutrition, Digestion, Metaboüsm 13 - Endocrinology, Neuroendocrinology, Neuropeptides - I 14 - Endocrinology, Neuroendocrinology, Neuropeptides - II 15 - Reproduction and Development 16 - Sensory Functions 17 - Brain and Behaviour 18 - Environmental Physiology 19 - Gravitational Physiology 20 - Advances in Animal and Comparative Physiology 21 - History of Physiology Satellite symposia of the 28th International Congress of Physiological Sciences 22 - Neurotransmitters in Invertebrates 23 - Neurobiology of Invertebrates 24 - Mechanism of Muscle Adaptation to Functional Requirements 25 - Oxygen Transport to Tissue 26 - Homeostasis in Injury and Shock 27 - Factors Influencing Adrenergic Mechanisms in the Heart 28 - Sahva and Sahvation 29 - Gastrointestinal Defence Mechanisms 30 - Neural Communications and Control 31 - Sensory Physiology of Aquatic Lower Vertebrates 32 - Contributions to Thermal Physiology 33 - Recent Advances of Avian Endocrinology 34 - Mathematical and Computational Methods in Physiology 35 - Hormones, Lipoproteins and Atherosclerosis 36 - Cellular Analogues of Conditioning and Neural Plasticity (Each volume is available separately.) ADVANCES IN PHYSIOLOGICAL SCIENCES Satellite Symposium of the 28th International Congress of Physiological Science Debrecen, Hungary 1980 Volume 30 Neural Communication and Control Editors Gy. Szιkel y Debrecen, Hungary E. Lαbos Budapest, Hungary S. Damjanovich Debrecen, Hungary m PERGAMON PRESS AKADΙMIA I KIADΣ Pergamon Press is the sole distributor for all countries, with the exception of the socialist countries. HUNGARY Akadémiai Kiadó, Budapest, Alkotmány u. 21. 1054 Hungary U.K. Pergamon Press Ltd., Headington Hill Hall, Oxford OX3 OBW, England U.S.A. Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, New York 10523, U.S.A. CANADA Pergamon of Canada, Suite 104, 150 Consumers Road, Willowdale, Ontario M2J 1P9, Canada AUSTRALIA Pergamon Press (Aust.) Pty. Ltd., P.O. Box 544, Potts Point, N.S.W. 2011, Australia FRANCE Pergamon Press SARL, 24 rue des Ecoles, 75240 Paris, Cedex 05, France FEDERAL REPUBLIC Pergamon Press GmbH, 6242 Kronberg-Taunus, OF GERMANY Hammerweg 6, Federal Republic of Germany Copyright © Akadémiai Kiadó, Budapest 1981 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, electrostatic, magnetic tape, mechanical,photo­ copying, recording or otherwise, without permission in writing from the publishers. British Library Cataloguing in Publication Data International Congress of Physiological Sciences. Satellite Symposium (28th : 1980 : Debrecen) Advances in physiological sciences. Vol. 30: Neural conununication and control 1. Physiology - Congresses I. Title IL Székely, Gy. III. Lábos, Ĺ. IV. Damjanovich, S. 591.1 QPl 80-42048 Pergamon Press ISBN O 08 026407 7 (Series) ISBN O 08 027351 3 (Volume) Akadémiai Kiadó ISBN 963 05 2691 3 (Series) ISBN 963 05 2755 8 (Volume) In order to make this volume available as ^economically and as rapidly as possible the authors' typescripts have been reproduced in their original forms. This method unfortunately has its typographi­ cal limitations but it is hoped that they in no way distract the reader. Printed in Hungary PREFACE In the surge of organization of the 28th International Congress of Phy­ siological Sciences, several colleagues from all over the world came to our help with their valuable suggestions about topics and subject matters of various symposia. Planning a satellite symposium with a theoretical neuro­ biology programme, we were especially glad to learn from Professor Donald M. MacKay's letter that the I. U. P. A. B. Commission for the Biophysics of Communication and Control decided to seek co-sponsorship from I. U. P. S. for a joint meeting. The Ust of invited participants and the final programme of the symposium became then the result of several letter exchanges and of a visit to Debrecen by Professor Peter I. M. Johannesma from the I. U. P. A. B. Commission. The title of this symposium reflects our joint intention of organizing an unconventional meeting to which scientists representing widely divergent fields of interest could be invited. The purpose was twofold. First, we wanted to avoid the drawbacks of the symposium of a self-contained scientific society, in which the participants are long familiar with each other's ideas and results. Second, we wanted to stimulate the exchange of information between a large variety of disciplines converging on the common endeavour to comprehend the brain. The Ust of invited participants comprised "experi­ mentalists" and "theorists"; and within the 3-day period of the symposium, we wanted to explore as many contact points as possible, around which profitable cooperation could crystallize in the future. In order to enlarge potential contact surfaces, we took the risk of embracing, even at the expense of the depth of our discussions, the widest possible area of neurobiology. Ted Bullock's brilliant introductory paper, showing the formidable versatility of nervous elements and systems on the phylogenetic scale, greatly contributed to the accomphshment of this pur­ pose. The subsequent papers were ordered according to a hierarchical scheme which started with studies on the excitable membrane and went on to the properties of a single neuron, of small and large neuronal ensembles and of systems of increasing complexity, considering physiological and anatomical aspects, as well as experimenting and modelHng. In the last session we arrived at whole-brain function as reflected in conscious experience, and in his fine concluding paper, Donald MacKay took us towards understanding the neural basis of cognitive experience through recent experiments on evaluative cogni- Vll tive agency in "split-brain" patients. The very active discussions, which were difficult to Stop, indicated that if not always real contact points, several "friction points" were found after each presentation. The book will show how much we succeeded, or failed, with our unconventional symposium. We want to express our gratitude to the City Coimcil of Debrecen and to the University Medical School of Debrecen for their generous support which rendered possible a homely accommodation and the creation of an in­ formal atmosphere for the symposium. The I. U. P. A. B. Commission for the Biophysics of Communication and Control contributed to travel ex­ penses. For the pubUcation of the book credit must go to the Publishing House of the Hungarian Academy of Sciences. Debrecen, August 1980 Gyφrgy Szιkely Elemιr Lαbos Sαndor Damjanovich viü OPENING REMARKS Donald M. MacKay In opening our proceedings, let me first express the indebtedness of us all to the University of Debrecen, and to the initiative of Professors Gy. Szιkely and S. Damjanovich, for making it possible for us to meet in such agreeable surroundings and with such excellent facilities for this some­ what unconventional experiment in cross-disciplinary communication. When the I. U. P. A. B. Commission for the Biophysics of Communication and Control decided to seek co-sponsorship from I. U. P. S. for such a meeting, it was a great pleasure to find that our ideas had already been laigely anticipated by these colleagues; and it is to them, together with Professor P. Johannesma of our I. U. P. A. B. Commission, that the bulk of the credit must go to the design and implementation of our programme. The purpose of our meeting is twofold. First, of course, we want to acquaint one another, as well as our disparities of discipline may permit, with what we see as good examples of the interstimulation of experiment and theory at our various levels of concern with neural communication and control. But secondly, and throughout this process, we want to ask ourselves what we can learn from this experience about the best ways to make experi­ ment and theory interfertile. In this respect, then, our aim might be called "metascientific". We must all have been dismayed by the proliferation of theoretical models of neural function over the past 30 years which have seemed to evoke little or no interest among experimental neuroscientists, and by the vast tracts of experimental data that have so far defied or failed to attract insightful theoretical analysis. Why has this been so? Are wfe perhaps in danger, on both sides, of being tempted by the availability of tools and funds into answering too many inadequately posed questions? Can we help one another to spot some of the more relevant questions we should be asking? Can we recognize any pointers towards a better working partner- iship between theory and experiment in our needy field? I do not suggest for a moment that brain research is peculiar among the sciences in this respect; but we are perhaps more sharply aware than in some of the longer-established disciplines of the need for an adequate conceptual framework, within which to design both our experiments and our theories. What does create problems of this kind for brain research, more than for most other sciences, is its multi-level structure. In this respect it is often compared with computer science. A computer chip, for example, can be IX analysed at the levels of atomic and molecular physics, or crystallography, or transistor circuitry, or information-processing logic. It can also be under­ stood in terms of its function as a component of a central processor, or as part of the embodiment of an "artificially intelhgent" agent. Between some of these levels (the molecular and the transistor levels for example) there are intimate practical relationships. Between others (such as the crystallographic and the programming levels) there are virtually none. The analogy is valid in so far as it brings out a distinction between two different kinds of traffic between experimentaUsts and theorists in brain research. First, at each given level (biophysical, neuronal, psychological), there is the usual need for theory to guide experiment and to be guided in return by results, with the same problems of securing interfertihty as in any other sciences. Over and above these, however, we have in brain research the problem of deciding with which other levels (if any) a given level of experi­ ment or theory should seek to interact. The computer analogy is sometimes used to suggest that the "higher" (more psychological) levels of analysis of brain function need have no more interest in the "lower" (physiological) than a computer programmer has in the electronics or physics of his machine. This however is an over-simpUfica- tion that neglects the functional relationships which can be obtained between factors at widely separated levels. Think for example of the biochemistry of mood-control, or the variety of levels at which we can identify functional parameters of interaction in a plexiform neuronal system. If the brain is to be compared at all to a computer, it must be to one whose programming can be affected (in ways not necessarily destructive of function) by a host of variables such as local changes in temperature or conductance, physical prox­ imity of related patterns of activity, overall balance of various supplies and the like. Certainly there can be no excuse for a neuroscientist working at any level to discount a priori the relevance of experiments or theories at another. Very well; but how does this work out in practice? What estabUshed theoretical skills (if any) are worth acquiring by someone interested in neural pommunication and control, and at what levels? Where (if anywhere) have experimental data accumulated in enough quantity and solidity to expose a theoretical model to a crucial test? Where (if at all) has theoretical or experimental work at one level led to insightful experimental design at an­ other? These are some of the questions that I hope we will address, expli­ citly or impUcitly, in our adventure the next few days. Ady. Physiol. Sei. Vol. 30. Neural Communication and Control Gy. Székely, Ε. Lábos, S. Damjanovich (eds) A COMPARATIVE NEUROLOGIST'S VIEW OF SIGNALS AND SIGNS IN THE NERVOUS SYSTEM Theodore Holmes Bullock Neurobiology Unit, Scripps Institution of Oceanography and Department of Neurosciences, School of Medicine, A-001 University of California, San Diego, La J olla, CA 92093, USA I. INTRODUCTION: AIMS, SLANT AND SCOPE I take it one of the prime questions in the communication aspect of neurobiology is "what are the signals actually employed in neural systems?" I take it we must look for them by measuring signs that something has been communicated. Therefore, an essential question that we must answer first, in order to come to the previous one is "what are the signs given by small pomponents of the system?" The qualification "small components" is necessary merely to remind us that all neural systems, as far as we know, consist of small components as the actual sensing and reacting elements. I am not ruling out, you'll note, that a massed potential for example from a piece of cortex could be a signal, but only reminding you that what detects and responds is not the cortex but cells of the cortex. The aims of this modest piece are to ask these two questions , in sequence. I take it that our brain is the product of a lot of evolution. Indeed it would seem obvious that no other system has come such a long way from the level exemplified in coelenterates, flatworms or even insects and gastropods to that of Einstein or Shakespeare, as has the nervous system. Therefore, it behooves us to maintain perspective and I propose to examine the two questions 'Vhat are the signs of response in -small components of the nervous system?" and 'Vhat are the signals actually employed in neural systems?" from a comparative standpoint. It is not only that we can expect clues and leads by studying simpler systems, or that some favorable material like the squid giant axon may help, but in addition the perspective itself, the act of comparing, the effort to discern trends or at any rate differences is sure to reveal insights we would miss otherwise. Further to expose my biases at the outset, the slant here will be pluralist, eclectic and empirical. That means I would rather notice and list than to overlook a phenomenon that could be a relevant sign or signal even if I can not explain it or fit it into a theoretical framework such as the sodium theory. I want to encourage theory and the development of a systematic frame of reference but even more I want to be sure we don,'t overlook relevant phenomena when we erect such structures. I believe that 1 2 as scientists we commonly exhibit our human limitations, one of which is a willingness to pay attention only to certain aspects of reality that impress us for some reason and to overlook or to take for granted, as not worth remark, a great deal that, may be quite germane but is outside of our normal domain of discourse. The scope of my effort today will be limited to those levels of neural events between major parts of a cell at a lower level and major parts of the brain at my upper limit. That means drawing lines to exclude molecules and organelles and membranes at one end and complex behavior, mentation or conscious experience at the' other. So much for aims, premise, slant and scope. Let me turn to the first question, about signs, that is, forms of response in cells and normal arrays of cells. II. SIGNS: FORMS OF RESPONSE The main result of a survey of animals, high and low, is that almost every possible sign is either to be found or is probable. I don't know of a nerve cell that luminesces or moves its pigment granules but the three main classes of response: chemical, electrical and physical are each represented by diverse specific examples. Chemical signs are generally the release of something if it's an organic molecule or else movement in either direction if it's an ion. I wonder vrtiether the former is limited to release just because it would be difficult to detect a transient uptake of a small quantity. What we can say, as a result of recent developments, is that the list of chemicals released in response to stimuli is long. There are not only the half dozen or so transmitters but a longer list of maybe fifteen or more different modulators and in addition a variety of metabolic by-products. Proteins are released by some nerve cells, so that the potential exists for a much longer list of specific substances. It's not my purpose to discuss the substances, the circumstances that cause their release or the meaning of the release, because the point that deserves emphasis here is that neurons have a lot of .ways of responding. It now appears clear that this reflects two different kinds of diversity. One is diversity of types of neurons - a diversity far larger than we used to think. The other is perhaps even farther from the usual textbook view, namely a multiplicity of substances released from single neurons. It is widely agreed now that neurons can release more than one transmitter, plus one or more modulators, plus several metabolites and sometimes proteins, neurosecretory or other special products. Our knowledge of most of these classes of substances in invertebrates is meager but it does permit us to say that variety of substances is not a monopoly of vertebrates. There may well be a flowering in the vertebrates, increasing the number of substances but we don't know that for sure. Electrical signs have classically been given as synaptic potentials leading to spikes which are essentially all alike. The evidence today requires us to paint quite a different picture· First, there is a variety of synaptic potentials; not only excitatory and inhibitory consequences distinguish them but several other properties. Some last about a millisecond, others up to at least ten. Some have a passive decay and are monophasic, others have a convex, partly active, decremental falling phase and some are distinctly biphasic. Some are facilitating others antifacilitating and there can be fast and slow phases of these effects of history. Amplitudes of course can be from vanishingly small up to an 2 overshooting 100 τπν· Then there is a whole spectrum of non-classical potentials such as the ILD's - inhibitions of long duration. Hyperpolarizations and depolarizations can be associated, not only with increased conductance, but with decreased conductance and possibly increased pump action. There is a class of relatively unfamiliar potentials called plateau potentials in which a neuron acts as though it has two states and can be flipped between them; one input flips it to the depolarizing plateau and another flips it back. There aré also other examples of regenerative hyper- or repolarizations, opposite in sign to the classical spike. We musn*t forget the local potential, a graded, local, active but not regenerative event. This may be important in axonal terminals and other situations, indeed in many axons it is one of the normal forms of action and in some the only form. These are the spikeless neurons. They are not necessarily amacrine, not even necessarily short axon neurons in the usual sense of intrinsic, Golgi type II cells with axons a few hundred microns long. The best studied spikeless neuron is in the legs of crabs and has a large axon from a centimeter to several centimeters long, depending on the size of the animal. A special form of graded and local potential that might be quite important but is little known even phenomenologically is the potential between points on the same cell, for example between dendrites and axon. How general this is or how large or how it changes with time and activity are hardly even studied since Gesell (19^0) claimed its importance more than forty years ago. I for one regard it as a neglected and possibly major cellular state variable which might be both an effect and a cause. Finally, there is a major category of potentials which is probably not one class in terms of mechanism, but heterogeneous. These are the oscillatory and more or less spontaneous potentials. They vary from extremely rhythmic to highly stochastic, from continuous, on-going autochthonous series to rapidly damped ringing, from nearly sinusoidal to quite spike-like. They may be signs of discrete inputs or of the prevailing steady state. They may act as though a single periodic process is at work or like relaxation oscillators. In short, the variety of electrical signs is formidable. Like the chemical, they differentiate a variety of distinct cell types but at the same time, a given neuron can use several of these forms of electrical signs. Notice that I have often used the word "cell" instead of neurons. This is to include the possibilities that glial cells may participate in some of the responses or signs of stimulation. Evoked potentials and ongoing potentials recorded from organized arrays of cells and gross brain structures are also signs of response and of activity states. They are presumably the volume conducted sum of cellular events of all the just mentioned kinds dependent not only on the mix of kinds but also on the relative timing or synchrony and on the geometry of the cells and processes. There might also be contributions from other sources such as vascular streaming potentials, potentials due to accumulation of ions in intercellular spaces, glial cell membrane potentials, and potentials between cerebrospinal fluid and intercellular fluids. These sources are primarily steady or only slowly changing and hence may contribute little directly to the conventionally filtered evoked or ongoing potentials of the brain. But some of them might on occasion change rapidly enough and the slow and infraslow potentials might be indirectly signs of brain states because the events of higher frequency content might depend on the level of standing potential. I would like to 3