SYNAPTIC AND EPHAPTIC TRANSMISSION 



189 



activity. The remo\al of inhibitory electrogenesis 

 either by drugs which specifically blockade hyper- 

 polarizing synapses, or by pathological conditions, 

 would then remove these brakes upon excitatory 

 activity and abnormal function would result. This 

 would be apparently caused by 'excitation' although 

 its fundamental mechanism would in reality be the 

 block of another, opposed type of synaptic activity, 

 the inhibitory electrogenesis. The pharmacological 

 classification of strychnine as a 'stimulant of the 

 central nervous system', already discussed, illustrates 

 the basic difference between a descriptive, phe- 

 nomenological classification and that ba.sed on 

 analysis of its mode of action. 



Phynulogical Effects of Different Proportions oj De- 

 polarizing and Hyperpolarizing Postsynaptic Potentials 



Apparently different physiological and pharma- 

 cological properties may result from different pro- 

 portions of the two kinds of synaptic activity. Thus, 

 the electrical activity of the cat cerebral cortex 

 differs profoundly from that of the cerebellar, but 

 these differences may be accounted for by the rela- 

 tively small degree of inhibitory electrogenesis ol the 

 cerebellar cortex (161-166). Pharmacological dif- 

 ferences, such as the insensitivity of the cerebellar 

 cortex to local applications of strychnine, are equally 

 ascribable to this quantitative factor. 



However, the response of the cerebellar electro- 

 cortical activity to different drugs depends upon 

 the mode of exciting that activity (Purpura, Girado & 

 Grundfest, in preparation; cf. also 99-101, 163). 

 Different cerebellopetal afferents may evoke po- 

 tentials of different forms at a single cortical site. 

 These potentials are composed of different propor- 

 tions of excitatory and inhibitory synaptic activities 

 as demonstrated by their different reactions to the 

 various specifically acting drugs. 



Synaptic Activity and Electrical Concomitants 



The matters discussed under this heading relate 

 physiological activity in the central nervous system 

 to the methodology of its study by electrophysiologi- 

 cal means. They are also considered by Frank in 

 Chapter X of this work. 



a) interpret.ations of changes in .'\mplitudes of 

 POSTSYNAPTIC POTENTIALS. Since p.s.p.'s are not 

 subject to refractoriness but are capable of summa- 

 tion and of being sustained, decrease in amplitudes of 

 p.s p.'s cannot be ascribed to their refractoriness or 



'occlusion'. A depolarizing p.s.p. therefore can 

 diminish only by virtue of the following factors. 



/) The conductile process of the preceding unit 

 is blocked by refractoriness. This is probably a minor 

 element since profound alterations in synaptic re- 

 sponses occur at frequencies of repetitive activity so 

 low that refractoriness of electrically excitable re- 

 sponses does not occur. 



2} The transmitter of the presynaptic terminals 

 may become exhausted or the receptor of the post- 

 synaptic membrane may become altered. The latter 

 factor has been discussed in connection with de- 

 .sensitization (p. 157). 



^) Stimulation at high frequencies may, however, 

 produce fused sustained p.s.p.'s that show little or 

 no fluctuation from the steady level (fig. gfi, C). 

 This effect probably develops when the synaptic 

 membrane is maximally excited by the frequently 

 released packets of transmitter agent. The steady 

 depolarization (or hyperpolarization) can be re- 

 corded in the cerebral cortex (cf. 176, fig. 10). 



4) Simultaneous and countervailing development 

 of hyperpolarizing p.s.p.'s may mask the depolariz- 

 ing. There is now considerable experimental evidence 

 that this factor is most important in the complex 

 synaptic organization of the central nervous system 

 (165-167). Indeed, the overt electrogenesis ob- 

 servable in the cerebral cortex after a single stimulus 

 may be only a small part of the total electrogenic 

 activity. The major part is not recorded because 

 depolarizing and hyperpolarizing p.s.p.'s are simul- 

 taneously produced and tend to cancel each other. 



b) interpretation OF electrotonic effects of 

 STANDING postsynaptic POTENTIALS. It has been 

 frequently assumed that the surface negativity of the 

 cerebral cortex caused by dendritic p.s.p.'s produces 

 anodal polarization of their cell bodies (cf. i 76, pp. 

 56 and 57). This conclusion is drawn from analogy with 

 the effects of externally applied currents, a cathode 

 on the surface depressing and a surface anode aug- 

 menting excitability of the cell bodies. This analogy 

 is not valid in the physiological case. Externally 

 recorded negativity means that the interior of the 

 generating site is depolarized (i.e. more positive than 

 the resting potential). Surface negative p.s.p.'s of 

 apical dendrites therefore must always act as an ex- 

 citatory (cathodal) stimulus for the electrically ex- 

 citable membrane of their cells (cf. 97, loi). 



c) synaptic transducer action AND electro- 

 genesis. The recorded electrical activity might even 



