Perspectives in Biology and Medicine

PROBLEMS OF PLASTICITY AND ORGANIZATION AT SIMPLEST LEVELS OF MAMMALIAN CENTRAL NERVOUS SYSTEM J. C. ECCLES, DMiI. {Oxon.), F.R.S.* I. Introduction When attempting to see in perspective future developments in our understanding ofthe mode ofoperation ofthe central nervous system, one naturally surveys past achievements. Ofcentral importance is the neurone theory, according to which each nerve cell or neurone functions as a unit which acts in an excitatory or inhibitory manner by means ofthe intimate contacts (synapses) which its branches make with other nerve cells. The neurone is a functional unit because transmission from its receptive sites (the synaptic endings on it) to its effector sites (the multitude of its own synaptic endings) occurs by the propagation ofan all-or-nothing impulse . The nature ofthis impulse in peripheral nerve fibers has now been defined in precise physicochemical terms (i, 2, 3, 4), and the available evidence (5) suggests that impulses in the central nervous system are similar, at least in essentials. Furthermore, the nature ofcentral synaptic transmission , both excitatory and inhibitory, is fairly well understood (5, 6). An outstanding gap is the identification ofalmost all the central synaptic transmitter substances, but it seems unlikely that any new principle will be involved in the operation of central synapses. Histological, physiological, and pharmacological investigations indicate that the central transmitters are liberated in the same way, probably from the synaptic vesicles in the presynaptic terminals, and act in the same manner as transmitters at peripheraljunctions . There are at least two, one being acetylcholine, and probably several more central excitatory transmitter substances. The selective effects of strychnine and tetanus toxin in suppressing inhibitory synaptic * Department ofPhysiology, Australian National University, Canberra, Australia. 379 action (5) lead to the postulate that central inhibitory transmission is due to a distinctive transmitter substance, but it is not yet certain that there is, uniquely, only one (5). Finally, in the generation of impulses, neurones in the central nervous system behave like the peripheral nerve and muscle cells, it being necessary merely that a certain level ofdepolarization be produced rapidly enough (7, 8,9). Thus we may with some confidence expect that future investigations will add detail to the picture that can now be sketched in outline for only a very few species ofcentral neurones (5). Furthermore, when we look beyond the behavior ofthe individual unit to the way neurones are linked together to give the co-ordinated and integrated behavior of the whole nervous system, we have reason to believe that at least the general principles have been established. For example, neurohistological investigation has revealed that nerve cells are organized in complex and specific patterns (10, 11, 12, 13, 14). Neurophysiologists have shown how the convergence ofmany excitatory pathways onto one neurone gives the summation of excitatory synaptic action which is required to make that neurone, in turn, fire an impulse and so exert a synaptic action on the several neurones comprising the next stage of the patterned behavior stemming from that neurone (5, 9, 15, 16, 17, 18, 19). As a physiological variant, convergence of inhibitory and excitatory synaptic action on any one neurone results in an algebraic summation of the opposed changes in membrane potential—hyperpolarization and depolarization , respectively—and the firing ofan impulse results only when the net depolarization is beyond the critical level for generating a discharge (5, 20). Since the operation of each unit of a neuronal pattern occupies only about one-thousandth ofa second and since each neurone has a nodal position in relation to several converging and diverging pathways, spatiotemporal patterns of unimaginable complexity and diversity would be woven in a fraction ofa second (19). Hence we have reason to believe that a sufficient explanation is available for the immense complexity and variety ofbehavior exhibited by animals with highly developed nervous systems. We are tempted to conclude that, in principle at least, the basic physiology ofthe nervous system has been established. The problems for the future would be to unravel the complexities ofthe neuronal connections to allow more and more complete understanding of the patterned behavior 380 J. C. Eccles · Mammalian Central Nervous System Perspectives in Biology and Medicine · Summer 1958 ofthe nervous system. This program ofinvestigation occupies by far the...