NEURON PHYSIOLOGY INTRODUCTION 



addition exert excitatory actions directly on other 

 neurons in the spinal cord (31, 32, 33, 35, 61, 62). 

 Until recently values for the central conduction time 

 of the so-called direct inhibitory pathway (annulo- 

 spiral afferent fibers to motoneurons of antagonist 

 action) were derived by measurements of the shortest 

 interval at which an inhibitory volley can precede a 

 monosynaptic excitatory volley and yet be eflfective in 

 inhibiting the reflex discharge. Since such intervals 

 approximated to zero, it was erroneously concluded 

 that the latency of direct inhibitory action approxi- 

 mated to that of monosynaptic excitatory action, and 

 hence that the inhibitory pathway was also monosyn- 

 aptic, i.e. that the annulospiral afTerents of muscle 

 had inhibitory synaptic endings on motoneurons (5, 

 28, 61, 64). However the IPSP generated under such 

 conditions has a latent period at least 0.8 msec. 

 longer than the monosynaptic excitatory action of a 

 comparable pathway (35), which is just the interval 

 that would be expected if there were a synaptic relay 

 on the inhibitory pathway. It has further been found 

 that the annulospiral afTerents establish a synaptic 

 relay in the interinediate nucleus which conforms in 

 every respect with the properties of the direct inhibi- 

 tory pathway (35)- Of particular significance is the 

 recent observation that the summed action of im- 

 pulses in several annulospiral fibers is required before 

 any IPSP is produced by them, which contrasts with 

 their monosynaptic excitatory pathway, where the 

 individual impulses are independently effective in 

 generating EPSP (36). Evidently the spatial summa- 

 tion of the inhibitory impulses also requires the 

 synaptic relay station that has been found in the 

 intermediate nucleus and that is required in explain- 

 ing the long central latency of the 'direct' inhibitory 

 pathway. The same additional latency and inter- 

 neuronal relay are observed for the IPSP generated 

 through the contralateral inhibitory pathway which 

 Wilson & Lloyd (78) have discovered in the Sj and 

 S3 segmental levels (20). Finally, the monosynaptic 

 excitatory action of afferent impulses from the quadri- 

 ceps and gracilis muscles on soleus and biceps-semi- 

 tendinosus motoneurons, respectively, (32) provides a 

 sufficient explanation of Sprague's observation (74) 

 that some afferent fibers entering by the L5 dorsal 

 root establish synaptic connections directly with 

 motoneurons of the L7 and Si segments [cf. Eccles 

 (29), p. 156]. It may therefore be taken as established 

 that a single interneuron is interpolated on the direct 

 inhibitory pathway, as shown diagrammatically in 

 figure g.-l. Similarly there is a single interneuron on 

 the inhibitory pathway from motor axon collaterals 



to motoneurons (34), as is shown diagrammatically 

 in figure gfi. By a systematic study of the IPSP's pro- 

 duced by afferent impulses in the fibers of Golgi 

 tendon organs, it has recently been found that there is 

 always at least one interneuron on the inhibitory 

 pathway, though sometimes two are interpolated (33)- 



Inhibitory and Excitatory Transmitter Substances 



Strychnine has been found to have a highly specific 

 and rapid action in depressing inhibitory synaptic 

 action (cf. Grundfest, Chapter V, fig. 12), at least 

 with the five types of inhibitory action that have so 

 far been investigated in the spinal cord (5, 18, 29). 

 Similarly, tetanus toxin very effectively depresses all 

 these inhibitory synaptic actions (9). In fact the 

 clinical effects of both strychnine and tetanus toxin 

 can be sufficiently explained by these actions. Since 

 the activation of the inhibitory interneurons is not 

 affected when synaptic inhibitory action has been 

 virtually abolished by strychnine or tetanus toxin, it 

 may be concluded that these agents exert their de- 

 pressant action on the inhibitory synapses, as indi- 

 cated in figure 9.4 and B. On account of the rapidity 

 and effectiveness of its action it seems likely that 

 strychnine acts competitively with the inhibitory 

 transmitter for the receptor patches of the inhibitory 

 subsynaptic membrane. Certainly the highly specific 

 actions of tetanus toxin and strychnine indicate that 

 inhibitory synaptic action is mediated by a specific 

 inhibitory transmitter substance. 



The interneuron on the inhibitory pathways (cf. 

 fig. 9.4 and E) can be regarded as being introduced in 

 order to change over from a neuron that manufactures 

 and liberates an excitatory transmitter substance to 

 one that operates through the inhibitory transmitter 

 substance. It is, therefore, postulated that any one 

 transmitter substance always has the same synaptic 

 action, i.e. excitatory or inhibitory, at all synapses on 

 nerve cells in the mammalian central nervous system. 

 According to this principle, any one class of nerve 

 cells in the mammalian central nervous system will 

 function exclusively either in an excitatory or in an 

 inhibitory capacity at all of its synaptic endings, i.e. 

 it is postulated that there are functionally just two 

 types of nerve cells, excitatory and inhibitory. The 

 interneurons illustrated in figure 9.4 and B are ex- 

 amples of 'inhibitory neurons'. On the other hand, 

 the dorsal root ganglion cells with their primary 

 afferent fibers, proi^ably the neurons of all the long 

 tracts both ascending and descending, the moto- 

 neurons, and many interneurons belong to the class 



