The Physiology of Synapses

John Carew Eccles

• Publisher: Academic Press
• Year: 2013
• Print ISBN: 9781483201030
• eBook ISBN: 9781483226064
• Topic: Biological Sciences
• Subtopic: Neuroscience
• Index: Biological Sciences

The Physiology of Synapses covers the considerable advances in understanding the complex physiology of synapses. This book is divided into 16 chapters that emphasize the mechanism of synaptic transmission. The first chapters describe the structural and physiological features of chemically transmitting synapses. The subsequent chapters deal with the excitatory postsynaptic responses to presynaptic impulse and the release of transmitter by presynaptic impulses. These topics are followed by discussions of the impulse generation by the excitatory postsynaptic potential; the postsynaptic electrical events produced by chemically transmitting inhibitory synapses; the ionic mechanism generating the inhibitory postsynaptic potential. The last chapters consider the mechanism of inhibitory transmitter substances, pathways responsible for postsynaptic inhibitory action, and the trophic and plastic properties of synapses. This book will prove useful to physiologists, neurologists, and researchers.

CHAPTER I

THE DEVELOPMENT OF IDEAS ON THE SYNAPSE

Publisher Summary

This chapter discusses the development of ideas on the synapse. When neurohistologists began to study the nervous system in detail, the complexity of the interlacing fiber structure led them to postulate that the nervous system was a complex net-like structure; this is the reticular theory of Gerlach. The resolving power of conventional light microscopy was inadequate to reveal the fine structure of the synapse at a level that was required to explain the physiological mechanism. When it was shown that a nerve impulse was followed by a prolonged state of hyperpolarization and an accompanying depression of excitability, it was proposed that inhibition was because of depression of interneurones that were common to the central inhibitory and excitatory pathways. Prior activation of some of these interneurones by the inhibitory volley would be followed by a prolonged depression, during which they could not be activated by the excitatory volley. Hence, the excitatory volley would be less effective in evoking the discharge of motoneurones. The experimental investigation of the mechanism by which synaptic excitatory action evokes the discharge of impulses is linked inseparably with the problem of the means by which a presynaptic nerve impulse evokes a postsynaptic depolarization.

A The conflict between the neurone theory and the reticular theory

When neurohistologists began to study the nervous system in detail, the complexity of the interlacing fibre structure led them to postulate that the nervous system was a complex net-like structure, which is the reticular theory of GERLACH (1871). The nerve cells were believed to be at the nodes of this reticular structure, and the nerve fibres originating from them branched profusely and anastomosed, so forming the fibre meshwork characteristic of grey matter (GOLGI 1885).

This interpretation was first challenged by HIS (1886, 1889) and FOREL (1887) who proposed instead that each nerve cell was an independent unit and that their branches did not anastomose, but merely entered into close contacts. His arrived at this conclusion from a study of the development of the nervous system from the individual neuroblasts, while FOREL was impressed by the selectivity of the atrophy of nerve cells after nerve fibres had been destroyed. Independently, RAMÓN Y CAJAL (1888, 1890a, 1890b, 1890c) had reached the same conclusions as a result of his investigations of embryonic material and of the intensive application of the Golgi technique, which stained specifically a very few nerve cells, that were thus revealed in their entirety and in isolation from all others. Other neurohistologists such as KÖLLIKER (1890), VAN GEHUCHTEN (1891) and v. LENHOSSÉK (1892, 1893) also strongly supported the theory of the independence of the nerve cells, which, following the suggestion of WALDEYER (1891), came to be known as the neurone theory, in contrast to the reticular theory.

Implicit in the neurone theory was the assumption that nerve cells must enter into functional connection with one another by contiguity, not continuity. As originally described by the neurohistologists this contiguity was achieved by the profusely branching nerve terminals which embraced nerve cells to form the baskets (corbeilles) and terminal brushes of RAMÓN Y CAJAL (1890a) and the “Fasernkörbe” that HELD (1891) first described in the trapezoid body. Fibres were also described interlacing with dendritic processes, such as for example the climbing fibres around the dendrites of the Purkinje cells (RAMÓN Y CAJAL 1890a) and in sympathetic ganglia (RAMÓN Y CAJAL 1909; DE CASTRO 1922, 1932). At first no differentiated terminals were distinguishable, probably because they were not developed in the very young animals that were investigated, and also because of the ineffectiveness of the Golgi technique in displaying the ultimate terminals. It remained for HELD (1897), AUERBACH (1898), RAMÓN Y CAJAL (1903), and WOLFF (1905) to demonstrate the characteristic “Endkörbe,” “Endfüße,” or “boutons” by which actual functional contact is achieved. It is convenient to use the term “synaptic knob” for the differentiated terminals of all kinds. Subsequently there was an intensive investigation of synaptic knobs with st udies of the details of morphology and distribution on a wide variety of neurones (cf. WINDLE and CLARK 1928; BARTELMEZ and HOERR 1933; BARR 1939; BODIAN 1937, 1940, 1942).

Nevertheless, despite the wealth of evidence against it (cf. RAMÓN Y CAJAL 1909), the reticular theory lingered on with the support of GOLGI (1890, 1891) and later of HELD (1905, 1909), who wrote in defence of it as recently as 1929. For example HELD (1905) believed that continuity between neurones was established by the fine neurofibrils that were described as passing from the synaptic knob to the underlying nerve cell. At that time neurofibrils were often believed to form the structural basis for transmission of impulses. Much detailed histological evidence was also adduced (cf. BIELSCHOWSKY 1928) that the synaptic knobs gave origin to a fine pericellular network of fibres, which established continuity with fine fibrils in the underlying nerve cell. This interpretation closely paralleled the periterminal reticulum which BOEKE (1911, 1932, 1940) described as subserving continuity across the neuromuscular junction. It is now recognized that these fine pericellular networks are non-nervous, and consequently they do not provide evidence for continuity between nerve cells (HINSEY 1934; NONIDEZ 1944).

In view of this continued support for the reticular theory, RAMÓN Y CAJAL (1934) was constrained to write his memorable last work in which he examined critically the whole controversy between the exponents of the neuronal and reticular theories. So effectively did he do this that the neuronal theory has not been seriously challenged since that time, though many of the old reticularists continued in their beliefs, or at least continued to claim that the neuronal theory was dead (cf. BOEKE 1940). The subsequent unassailable position of the neurone theory has been well described by BODIAN (1942, 1952) and NONIDEZ (1944). It has received strong support from degeneration experiments which showed that after section of a presynaptic pathway there was degeneration of the synaptic knobs, but not of the postsynaptic structure (HOFF 1932; FOERSTER, GAGEL and SHEEHAN 1933; SCHIMERT 1939), and that after axon section the retrograde degeneration did not involve the synaptic knobs in contact with the degenerated neurone (BARR 1940; SCHADEWALD 1941, 1942).

The resolving power of conventional light microscopy was inadequate to reveal the fine structure of the synapse at a level that was required to explain the physiological mechanism. As techniques improved, the synaptic knobs appeared to be more closely attached to the postsynaptic membrane (cf. WYCKOFF and YOUNG 1956); so much so that there was thought to be just one membrane shared by the pre- and post-synaptic structures (BODIAN 1952). Such an arrangement was not acceptable as an efficient device for chemical transmission.

However, as described in Chapter II, the higher magnification given by electron microscopy has revealed that the presynaptic and postsynaptic membranes are two separate membranes about 70 Å thick, and that they are...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• PREFACE
• ACKNOWLEDGEMENTS
• SYMBOLS AND ABBREVIATIONS
• Chapter 1: THE DEVELOPMENT OF IDEAS ON THE SYNAPSE
• Chapter 2: STRUCTURAL FEATURES OF CHEMICALLY TRANSMITTING SYNAPSES
• Chapter 3: PHYSIOLOGICAL PROPERTIES OF CHEMICALLY TRANSMITTING SYNAPSES IN THE RESTING STATE
• Chapter 4: EXCITATORY POSTSYNAPTIC RESPONSES TO PRESYNAPTIC IMPULSES
• Chapter 5: EXCITATORY TRANSMITTER SUBSTANCES
• Chapter 6: THE RELEASE OF TRANSMITTER BY PRESYNAPTIC IMPULSES
• Chapter 7: THE GENERATION OF IMPULSES BY THE EXCITATORY POSTSYNAPTIC POTENTIAL AND THE ENDPLATE POTENTIAL
• Chapter 8: THE PRESYNAPTIC TERMINALS OF CHEMICALLY TRANSMITTING SYNAPSES
• Chapter 9: EXCITATORY SYNAPSES OPERATING BY ELECTRICAL TRANSMISSION
• Chapter 10: THE POSTSYNAPTIC ELECTRICAL EVENTS PRODUCED BY CHEMICALLY TRANSMITTING INHIBITORY SYNAPSES
• Chapter 11: THE IONIC MECHANISM GENERATING THE INHIBITORY POSTSYNAPTIC POTENTIAL
• Chapter 12: INHIBITORY TRANSMITTER SUBSTANCES
• Chapter 13: PATHWAYS RESPONSIBLE FOR POSTSYNAPTIC INHIBITORY ACTION
• Chapter 14: INHIBITORY SYNAPSES OPERATING BY ELECTRICAL TRANSMISSION
• Chapter 15: PRESYNAPTIC INHIBITION
• Chapter 16: THE TROPHIC AND PLASTIC PROPERTIES OF SYNAPSES
• EPILOGUE
• REFERENCES
• SUBJECT INDEX