History of the synapse

351 Pages·2001·10.332 MB·English

by  Bennett, M. R

History of the Synapse
Dedicated
to
Bernard Katz
and to the memory of
John Newport Langley
History of the Synapse
Max R.Bennett
University of Sydney, Australia
harwood academic publishers
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ISBN 90-5823-233-6 (Print Edition)
Cover: Hippocampal neuron stained for MAP together with synaptotagmin. Courtesy M. Matteoli and © Cell Press.
2
Cover design by Lee McLachlan.
Contents
Introduction ix
Chapter 1 The early history of the synapse: from Plato to Sherrington 1
1.1 Plato and Aristotle: ‘vital pneuma’ is necessary to initiate organ function 1
1.2 Galen: pneuma is conducted and transmitted from nerve to muscle 3
1.3 Descartes: the replacement of pneuma by mechanical corpuscles 4
1.4 Borelli: a corpuscular description of conduction and transmission 6
1.5 Fontana: nerves are composed of many cylinders along each of which conduction occurs 8
1.6 Galvani: electricity is conducted and transmitted not corpuscles 9
1.7 Matteucci and du Bois-Reymond: transient electrical changes are conducted (the action potential) 12
1.8 Helmholtz: the action potential has a finite velocity 15
1.9 Kuhne and Auerbach: identifying the structure of nerve endings on muscle and neurons 16
1.10 Cajal: nerve endings are not continuous with the cells on which they impinge 18
1.11 Sherrington: the adoption of the word ‘synapse’ 22
Chapter 2 Emergence of the concept of transmitter release at peripheral and central synapses 26
2.1 Research on the synapse in the laboratories of Sherrington and Langley before the Great War 26
2.2 Sherrington’s concept of the inhibitory and excitatory states of central synapses 28
2.3 Lucas, Adrian, and the electrical concept of the inhibitory state of central synapses 29
2.4 Loewi, Dale and Eccles examine the inhibitory state at autonomie neuromuscular junctions 32
2.5 Eccles develops the electrical concept of the excitatory state at autonomie synapses 32
2.6 Katz, Kuffler and Eccles establish the motor endplate as the paradigm synapse for electrophysiology 35
2.7 Eccles elucidates the electrical signs of the inhibitory and excitatory states of central synapses 36
2.8 Katz’s concept of quantal transmitter release at the motor endplate and the vesicle hypothesis 39
2.9 Conclusion: the establishment of Sherrington’s concept of the synapse in the central nervous system and 41
central synaptic transmission
Chapter 3 The discovery of acetylcholine and the concept of receptors at synapses 43
3.1 Introduction 43
3.2 Claude Bernard and curarization: the notion of an intermediate zone between nerve and muscle 44
3.3 Paul Ehrlich and the idea of the ‘receptive side chains’ of cells 46
3.4 John Langley and T.R.Elliott: the emergence of the concept of chemical transmission between sympathetic 46
nerves and smooth muscle
3.5 The action of curare and John Langley’s development of the idea of transmitter receptors 51
3.6 The Langley-Ehrlich receptor theory 54
vi
3.7 The discovery of acetylcholine and its physiological action at autonomic neuroeffector junctions 54
3.8 The physiological action of acetylcholine in autonomic ganglia 59
3.9 The identity of acetylcholine as the transmitter substance at somatic neuromuscular junctions 60
3.10 The discovery of the physiological action of single acetylcholine receptors 61
3.11 Conclusion 64
Chapter 4 The discovery of adrenaline and the concept of autoreceptors at synapses 65
4.1 Introduction: the discovery of noradrenaline as a transmitter 65
4.2 Early observations leading to the idea of autoreceptors 65
4.3 Direct experimental evidence for autoreceptors 68
4.4 Identification of presynaptic adrenergic autoreceptors different from postsynaptic adrenergic receptors 71
4.5 Presynaptic adrenergic autoreceptors in the central nervous system 72
4.6 Evidence that endogenous autoreceptor mechanisms exist 72
4.7 The ionic basis of the action of alpha 2 adrenoceptors 73
4.8 Conclusion 76
Chapter 5 The discovery of amino acid transmission at synapses in the central nervous system 77
5.1 Introduction 77
5.2 Identification of excitant and depressant amino acids 77
5.3 Glycine accepted as an inhibitory transmitter in the spinal cord 78
5.4 The emergence of GAB A as an inhibitory transmitter in the brain 81
5.5 L-Glutamate as a neurotransmitter: synaptic excitation, ion fluxes and neurotransmitter transporters 84
5.6 NMDA receptors: the first amino acid receptor identified at central excitatory synapses 86
5.7 Non-NMDA receptors at excitatory synapses 87
5.8 GAB A receptors 87
5.9 Conclusion 87
Chapter 6 Monoaminergic synapses and schizophrenia: the discovery of neuroleptics 90
6.1 Introduction 90
6.2 Chlorpromazine 90
6.3 Haloperidol 91
6.4 The dopamine hypothesis for neuroleptics 91
6.5 Dopaminergic projections in the brain 92
6.6 Identification of the D -like and D -like dopamine receptors 92
1 2
6.7 Determination of different classes of dopamine receptors 95
6.8 Clozapine 95
6.9 Distribution of D and D receptors in the striatum of schizophrenics 98
1 2
6.10 Mixed aminergic actions of the neuroleptics: serotonin and dopamine receptor blockade 1 02
6.11 Cellular and molecular mechanisms of action of dopamine receptors 1 02
6.12 The time course of action of neuroleptics on dopamine receptors and the emergence of antipsychotic effects1 03
vii
6.13 Conclusion 1 04
Chapter 7 The discovery of transmitters other than noradrenaline and acetylcholine at synapses in the 1 05
peripheral nervous system
7.1 Introduction: J.N.Langley, H.H.Dale and non-adrenergic, non-cholinergic (NANC) transmission 1 05
7.2 Parasympathetic neuromuscular junctions in the gastrointestinal tract: mechanical studies 1 09
7.3 Parasympathetic neuromuscular junctions in the gastrointestinal tract: electrophysiological studies 1 16
7.4 NANC transmission: the new autonomic paradigm 1 21
7.5 Contemporary views on the identity of NANC inhibitory transmitters 1 27
7.6 Ionic mechanisms involved in generating the IJP 1 32
7.7 The secretion of NANC transmitters responsible for the IJP 1 33
7.8 NANC excitatory transmission in the gastrointestinal tract 1 34
7.9 Conclusion 1 35
Chapter 8 Development of the concept of a calcium sensor in transmitter release at synapses 1 36
8.1 Introduction 1 36
8.2 Calcium is necessary for the release of transmitter 1 36
8.3 Electrophysiological evidence that calcium is necessary for the release of transmitter: the concept of a 1 37
calcium sensor for secretion
8.4 The calcium action potential 1 40
8.5 Are calcium movements across the nerve terminal necessary for evoked secretion? 1 43
8.6 Direct evidence for calcium entry across the nerve terminal membrane during an impulse 1 47
8.7 Calcium channels in the nerve terminal 1 49
8.8 Identification of the calcium sensor molecule 1 58
8.9 Conclusion 1 62
Chapter 9 The discovery of quantal secretion and the statistics of transmitter release at synapses 1 64
9.1 Introduction 1 64
9.2 Evoked quantal release as a binomial or Poisson variate 1 65
9.3 Kinetics of release of a quantum 1 76
9.4 Maximum likelihood estimation of parameters in statistical models of quantal release 1 86
9.5 Autocorrelation function used to detect quantal release 1 90
9.6 Model discrimination: statistical methods for discrimination between different statistical models of 1 93
transmitter release
9.7 Appendix 1 95
Chapter The discovery of long-term potentiation of transmission at synapses 2 16
10
10.1 Introduction: the hippocampus, memory and long-term potentiation (LTP) 2 16
10.2 LTP at synapses in the brain 2 19
10.3 The induction of associative LTP in the brain 2 20
10.4 The maintenance of associative LTP 2 26
10.5 Biochemical pathways implicated in the maintenance phase of associative LTP 2 29
viii
10.6 Evidence that associative LTP is involved in memory 2 30
10.7 The induction of non-associative LTP 2 33
10.8 Summary and Conclusion 2 33
Chapter Emergence of the concept of synapse formation molecules 2 38
11
11.1 Introduction 2 38
11.2 Synapse formation in muscle 2 38
11.3 Synapse formation molecules in muscle and the elimination of polyneuronal innervation 2 43
11.4 Elimination of polyneuronal innervation during muscle development described by dual-constraint theory 2 47
11.5 Elimination of polyneuronal innervation during reinnervation of muscles described by dual-constraint theory 255
11.6 Elimination of polyneuronal innervation and establishment of topographical maps in muscle described by 2 62
dual-constraint theory
11.7 Identification of the synapse formation molecules 2 71
11.8 Synapse formation in autonomic ganglia 2 79
11.9 Elimination of polyneuronal innervation in autonomic ganglia 2 79
11.10 Elimination of polyneuronal innervation during reinnervation of ganglia 2 80
11.11 Identification of synapse formation molecules in autonomic ganglia 2 81
11.12 Conclusion 2 82
Epilogue 2 86
References 2 88
Illustration Acknowledgements 3 28
Acknowledgements 3 32
Index 3 34
Introduction
This work is an attempt to provide a history of those discoveries concerning the identification and function of synapses which
provide the foundations for research during this new century. It is written in the conviction that errors in the development and
application of contemporary concepts to the understanding of synapses arise if there is failure to probe the origins of the
scientific paradigm at present in use. The idea that blood vessels are the means by which muscles are activated lasted some
five hundred years, from Aristotle in the fourth century BC to Galen in the second century AD, when it was shown that nerves
are the means of communication to muscle. The concept that the ventricles of the brain, containing the psychic pneuma
identified by Aristotle, are the sites at which sensations, thinking and memory are experienced lasted for a much longer period.
The most posterior ventricle was taken as initiating the flow of psychic pneuma to the nerves and hence to muscles for their
activation. This concept lasted for over fifteen hundred years, from shortly after Galen to Thomas Willis at the end of the
seventeenth century. Is the historical development of these facts, involving both the discoveries and thoughts of men of
genius, to be regarded as an oddity divorced from ‘the common-sense’ which we now bring to the solution of problems
regarding the workings of synapses? The first chapter considers the wonderful story, evolving over two and a half thousand
years, of how progress was made in the establishment of a conceptual structure that would allow the synapse to be identified
at the beginning of the twentieth century. It was founded on the idea of conduction and transmission to muscle by Aristotle,
the identification of nerves as providing the conducting medium by Galen and on Galvini’s discovery that it is electricity that
is conducted, not Cartesian corpuscles. The concept of the synapse which was accepted for most of the twentieth century, was
certainly not in place at the end of the nineteenth century through the work of Sherrington, as is popularly accepted. Rather,
he highlighted the fact that a mechanism must be sought by which conduction could proceed from one excitable cell to another
following the discovery of Cajal that neurones are separate cells. However, this difficulty had been a focus of physiological
enquiry for centuries, particularly to Galen and to Descartes’ contemporary Borelli. In naming this region of apposition
between excitable cells ‘the synapse’ Sherrington helped focus the physiological enquiry which was to be so brilliantly
brought to fruition by his mentor at Cambridge, John Newport Langley.
The genius of Langley is exemplified in the experiments he performed. These first drew attention to the similarities
between the effects of sympathetic nerve stimulation on autonomic effectors and that of extracts of the adrenal glands, leading
to the audacious speculation of his student Elliott that electrical conduction is transmitted chemically and that in the case of
sympathetic nerves this chemical is adrenaline (Chapters 2 and 3). However, a reading of the papers of that period (the beginning
of the twentieth century) points up that it was Langley’s discovery of transmitter receptors at the somatic neuromuscular
junction that was the pivotal work in establishing the concept of the synapse. Langley championed the idea of the receptor in
the face of fierce opposition, particularly from the founder of immunology, the chemist Paul Ehrlich. It was Langley’s work
that gave us the modern concept of the synapse, namely an area of apposition between a nerve ending and another cell at
which a chemical substance is released from the ending onto a ‘receptive substance’ found on the cell. All of these definitive
concepts which gave ‘substance’ to the abstract term ‘synapse’ were established in a period of about eight years, principally
from the one laboratory! The subsequent identification of acetylcholine as the chemical released from motor nerve terminals
had to wait several more decades (Chapter 3). It was primarily the laboratory in London of Dale, a former student of Langley,
together with that of Loewi in Germany that was then responsible for generalising the principle of chemical transmission at
peripheral synapses.
The study of central synaptic transmission did not reach a level of sophistication comparable to that at peripheral synapses
for nearly half a century after the period when the idea of transmitter substances and their receptors was first conceived. The
1950s were a remarkable period for central synaptic transmission. First amino-acids were identified as likely central
transmitters (Chapter 5) and then neuroleptic agents were synthesised and shown to act at central monoaminergic synapses in
ways which were to have a profound impact on the alleviation of mental suffering, such as in schizophrenia (Chapter 6). It was
also at this time that the mechanism of synaptic transmission was greatly illuminated due to introduction of the glass
microelectrode for studying the same junction that gave us the concept of the receptor, namely the somatic neuromuscular
junction. Katz and his colleagues showed that transmitter release occurs in units (Chapter 9) and that the probability of release