Robert E. Burke. Laboratory of Neural Control, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20895, USA.
Abstract
This chapter deals with the central role that Sir John Eccles played in the elucidation of the mechanisms of synaptic transmission within the central nervous system during the three decades between the late 1930s and 1966. His seminal discoveries involved studies of synaptic input to spinal motoneurons using intracellular recording via glass micropipettes after their introduction in the late 1940s. After defending the hypothesis that electrical currents alone explained central synaptic events, his observations of reversal potentials and sensitivity to ion injections instantly converted Eccles to the idea that central synapses generate postsynaptic potentials, designated IPSPs and EPSPs, by liberating chemical transmitters. He and his collaborators used pharmacological manipulations of recurrent inhibition to support the idea that a given neuron liberates the same chemical transmitter substance at all of its synapses, which he called ‘‘Dale’s Principle’’. His team worked out the mechanisms and spinal circuits underlying disynaptic and recurrent inhibition, as well as those of presynaptic inhibition. Not content with the view that central synapses were static entities, Eccles also made seminal observations on synaptic plasticity induced by alterations in use and disuse. Although his firmly held belief that the extensive dendritic trees of motoneurons were essentially irrelevant to synaptic events at the soma was later refuted by others in the mid-1960s, Eccles stands as a towering figure in the history of neuroscience. His prodigious energy and commanding intellect gave the field of central synaptic transmission the conceptual bases that have guided it for over 40 years.
Introduction
‘‘If I have seen further it is by standing on ye shoulders of Giants.’’ Isaac Newton to Robert Hooke, 5 February, 1676. Without doubt, Sir John Carew Eccles (1903–1997) is one of the giants upon whose shoulders all neuroscientists now stand. In no area is this truer than the understanding of the basic mechanisms that underlie synaptic transmission within the central nervous system (CNS). During the first half of the 20th century, the consensus among neurophysiologists was that synaptic transmission involved direct transfer of electrical potentials through synapses between neurons. Although it was clear that such transmission would have to involve movement of ions rather than electrons, the idea was embodied as a theory of ‘‘electrical transmission’’. Until 1950, there was no more vigorous proponent of this idea than Eccles. This changed quite dramatically when Eccles applied the newly introduced glass micropipette electrode to record from spinal motoneurons. He moved immediately away from arguments based on extracellular fields to directly demonstrate that spinal cord synapses exhibited synaptic delays, reversal potentials, pharmacological and ionic sensitivity, and short-term plasticity that all indicated a purely chemical mechanism. For these achievements, Eccles was awarded the Nobel Prize in Physiology/Medicine in 1963, jointly with Alan Hodgkin (1914–1998) and Andrew Huxley. This essay concentrates on Eccles’ critical contributions to unraveling the mechanisms of central synaptic transmission during the period from 1930 to around 1964, when Eccles published his magisterial monograph on synaptic mechanisms (Eccles, 1964).
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