Introduction

It was DECARTES who first introduced the notion of inhibition in the physiology of nervous system. The idea of inhibition is a counterpart of the excitation in the physiology of the nervous system. The notion of excitation has been the central idea of neurophysiologists and neuroanatomists for the past century. Fortuitously they have been exclusively concerned with the excitatory activity of neurons, nerve fibers and muscles without paying any special attention to the inhibitory action of the nervous system. It is interesting to note that, despite CAJAL’S commanding understanding of the structure of nervous system, he failed to recognize the existence and accordingly the importance of inhibitory neurons. He thought that the nervous system consisted exclusively of neurons specialized for excitatory action. It was pointed out by ECCLES (1964) that the CAJAL’S diagrams and those of his student, LORENTE DE NÓ (1934) showed no inhibitory synaptic action. SHERRINGTON’S ingeneous insight into the physiology of central nervous system (CNS) gave rise to two opposite conceptions concerning the reflex activity, excitation and inhibition of the CNS of mammals.

The term “synapse” was first introduced by SHERRINGTON (1897) into the physiology of the CNS. The development of synaptology as a major neurobiological discipline may be traced to two conceptual formulations, the reticular theory and the neuron doctrine. Nineteenth century histologists, upon examining the CNS with the light microscope, came to the idea that the nerve fibers in the CNS made profuse branching and these branches gave rise to profound anastomosing syncytial networks without interruption. This is the reticular theory which was first proposed by GERLACH (1871) who assumed that the nerve cells were situated at the nodes of the reticular structures. GOLGI (1885) adopted the same notion and expanded it to the general structure of the CNS. His conviction in the reticular theory was so strong as to make one believe that he was a real founder of the notion of the reticular structure of the CNS. His (1886, 1889) and FOREL (1887) proposed the idea that each nerve cell was isolated unit and its axon and branches did not anastomose, but merely entered into close contact in some way or other. It is historically remarkable that the most powerful opponent of the reticular theory was Ramón y CAJAL (1888, 1890 a, b, c) who, applying intensively GOLGI technique to the study of the structure of the CNS, had reached the same conclusion as proposed by the latter. It might be useless to cite all histologists who followed CAJAL to trace the history of impact between two schools, reticular theorists and neuron theorists. It was the neuron theory that insisted that nerve cells must enter into functional connection with one another by contiguity, but not by continuity. The notion of continuity of the neuronal networks was proposed by the reticular theorists who insisted that the nervous system was the endless meshworks with syncytial connections in the CNS. With the support of GOLGI, the reticular theory lingered on until as recently as 1925 when HELD (1905, 1909) was compelled to write in defense of the neuron theory. In view of this long lasting support for the reticular theory, CAJAL (1934) was also compelled to defend the neuron theory by examining critically the whole controversy between two rival theories. In spite of his unchallengeable criticisms, the old reticularists continued to believe in their hypothesis until as recently as 1940 when BOEKE (1940) reviewed the questions of neuroanatomy of the time. The observation of neurofibrils which were discovered by classical light microscopists in mid 18th century and have been investigated until the present time gave rise to the neurofibril hypothesis of the nervous system which held that neurofibrils were continuous from cell to cell and vital in impulse transmission. Throughout the first third of the 20th century a controversy was rampant over whether the neurofibrils were or were not continuous from cell to cell, and whether they were or were not involved in conduction or transmission in the nervous system. At the end of this period it was finally agreed that these fibrous structures in nerve were real and not fixation artifact (BOZLER, 1927; WEISS and WANG, 1936). By the advent of the electron microscope, however, it was definitely clarified that the neurofibrils were not continuous from cell to cell but were disrupted by 200 Å cleft at the synapse. Thus finally the reticular theory had to disappear. BODIAN (1942, 1952) and NONIDEZ (1944) must be cited as final unassailable defenders of the neuron theory, because they obtained one of the most convincing evidences of neuron theory from degeneration experiments. They showed that when the nerve fibers were sectioned the distal parts of the fibers degenerated up to the end of the fibers, but the degeneration did not spread beyond. This fact clearly demonstrated that in some way or other discontinuity exists in the CNS and a neuron is an isolated functional unit. It was as late as 1954 that the neuron theory was decisively established morphologically by the aid of the electron microscope, because the resolving power of the light microscope was inadequate to disclose the fine structure of the synapse at the level that was required to explain the electrophysiology of transmission of nerve impulses. It was the advent of the electron microscopy that unquestionably established the neuron theory, the reticular theory being completely abolished. At two hundreds Angstroms cleft between presynaptic and postsynaptic membranes was revealed by PALADE and PALAY (1954), PALAY (1956), De ROBERTIS (1956), De ROBERTIS and FRANCHI (1956), who completely wiped out all doubts about the structural discontinuity of the synapse. Structural assymmetry at the synapse was confirmed electron microscopically and the functional polarity of it was also revealed electrophysiologically. The impulses conduct unidirectionally at the synapse. Two way conduction takes place in the nerve fibers but not at the synapse. The higher resolving power provided by the electron microscope has allowed us to study the synapse at a level which was not attainable with the light microscope. We are now in the stage where we can obtain meaningful correlations between structure and function of the nervous system. The development of sophisticated techniques for intracellular recording of the nervous activity in the 1950’s led to an important advance in the concepts of neuronal functions. It became possible to penetrate a microelectrode into the cytoplasm of neurons through the excitable membrane without grossly damaging to the cell. It was revealed that the inside of the neuron is about 80 millivolts negative to the outside. It also became clear that this potential difference is the results of the selective distribution of ions across the semipermeable membrane. Excitatory and inhibitory synaptic potentials were found to consist of small depolarization and hyperpolarization of the postsynaptic membrane respectively caused by the different kinds of transmitter substances which are released from the nerve endings of the presynaptic fibers at the time of the arrival of nerve impulses.

The term “synapse” was merely introduced by SHERRINGTON (1897) to denote the specific physiological activity at a supposed junctional site. On a priori grounds it is unnecessary that a set of distinct structural specialization should be present. There is no theoretical necessity to identify specialized structure at synapses because communications between nerve cells might occur at morphologically non-specialized interface by ephaptic transmission or some other kinds of mechanisms. But, electrophysiology and electron microscopy surpassed such intriguing arguments, identifying morphological and functional entity of synapses unequivocally. The facts that synapses clearly exhibit certain well-defined structure and that these structural specializations can reflect the functional nature of...