I50 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



wherever synapses occur. These junctional regions 

 also appear to have special biochemical requirements. 

 Transmission, for example, is more easily disrupted 

 by anoxia than is conduction. Pharmacological and 

 biochemical tools, particularly in combination with 

 the techniques of electrophysiology, provide additional 

 data on the processes of synaptic transmission (cf. 

 96, 99-101, 161-166). 



A challenge to the electrical theory was offered by 

 that of chemical transmission which evolved chiefly 

 from the work of Dale, Loewi, Cannon and their 

 associates (cf. 150, 177). According to this view, 

 activity of a presynaptic fiber releases at its synaptic 

 terminals a chemical transmitter agent. That sub- 

 stance excites the electrical activity of the postjunc- 

 tional cell. By repetition of the secretory process at 

 the terminals of the latter, a new action is started in 

 the next unit of a transmissional chain. The present 

 chapter adopts this view. 



The conclusion that synaptic transmission obliga- 

 torily involves a chemical mediator derives from a 

 hypothesis based upon a recent examination of data 

 on available synaptic systems (97). All possess a com- 

 mon constellation of properties that are shown in 

 table I and discussed in the portion of this chapter 

 devoted to synaptic electrogenesis. The entire group 

 of these distinguishing characteristics appears to be 

 referable to a single fundamental property of synaptic 

 electrogenic membrane, namely that its activity is 

 not initiated by an electrical stimulus. Thus, there 

 arises a profound distinction between the conductile 

 activity of axons or muscle fibers and the transmis- 

 sional activity at synapses. The former is electrically 

 excitable by an applied stimulus or by the internally 

 generated local circuit of activity. The latter is elec- 

 trically ine.xcitable and must be evoked by a specific 

 stimulus which in the context of synaptic structure 

 must be a chemical excitant, or transmitter agent, 

 released by the active presynaptic nerve fibers. 



The currently used definition of synapses is still 

 essentially as it developed with Sherrington and 

 Ramon y Cajal, a junction in contiguity between 

 anatomically distinct cells across which activity is 

 nevertheless transmitted, but only in one direction, 

 from the presynaptic cell to the postsynaptic. Many 

 other specifications are now available to distinguish 

 transmissional activity from conductile or ephaptic, 

 and these appear to derive from the one feature, that 

 synaptic activity is electrically inexcitable. 



N.-VTURE OF PDSTSYN.\PTIC PGTENTI.^LS 



The earlier studies of p.s.p.'s were made with 



external recordings from muscle endplates (59, 6q, 

 63, 86), sympathetic ganglia (56) and the spinal cord 

 (57' 58)- The muscle synapses being more easily 

 accessible, it was most intensively studied both 

 electrophysiologically and pharmacologically (cf. 

 62). More recently, this and many other varieties of 

 synapses have been investigated with intracellular 

 recording (cf. 52, 59, 60, 68, 95, 97), and a reasonably 

 coherent and satisfactory description of the principles 

 of synaptic electrogenesis is now available. 



Generation Sites of Postsynaptic Potentials 



As noted above, p.s.p.'s are associated with the 

 occurrence of transmissional activity at junctions 

 between a pre- and a postunit. Only in a few systems 

 (e.g. neuromuscular and squid giant axon synapses) 

 is the junction confined to a clearly delineated area of 

 the postunit. In these cases it is found that the p.s.p. 

 is largest within the region of the junction and de- 

 creases rapidly as the distance of the recording 

 electrode from the junction increases (fig. 2). The 

 form of the potential is also distorted in the manner 

 characteristic of electrotonic spread (114, 141), both 

 facts indicating that the site at which electrogenesis 

 occurs is confined to the synaptic region. As will be 

 described below, the nonpropagating, 'standing' 

 response of p.s.p.'s is a consequence of electrical 

 inexcitability. 



When the p.s.p. is recorded with a microelectrode, 

 at first externally and then internally, the sign of the 

 p.s.p. reverses when the electrode penetrates the cell. 

 Like the spike, which also undergoes reversal of sign 

 under the same conditions, the neurally evoked po- 

 tential is produced at the excitable electrogenic 

 membrane of the postjunctional cell, hence the term 

 p.s.p. 



Molecular Structures of Differently Excitable Membranes 



The structures of the membranes that are involved 

 in ssnaptic activity are not as yet known. The pre- 

 synaptic terminals occur in an immense variety of 

 shapes and sizes. In some of these electron microscopy 

 has indicated the presence of vesicles (54, 174). The 

 latter have been interpreted (cf. 52) as sites of concen- 

 tration of chemical mediators which presumably are 

 formed in the nerve fibers and ejected during activity 

 into an extracellular synaptic space of about 100 A. 

 The postsynaptic sites which respond specifically to 

 the chemical transmitter agents cannot, at present, be 

 differentiated structurally from those of electrically 

 excitable membranes. This is perhaps l^est exemplified 



