70 



HANDBOOK OF PHYSIOLOGY 



NEUROPHYSIOLOGY I 



residual action. By investigating the effects of varying 

 the membrane potential by current applied through 

 the microelectrode (cf Grundfest, Chapter V, fig. 1 2), 

 it has been shown that the IPSP is produced by a 

 process of ionic diffusion across the subsynaptic 

 membrane that has an equilibrium potential at about 

 10 mv more hyperpolarized than the resting mem- 

 brane potential, i.e. at about —80 mv (16). Further- 

 more, it has been shown by ionophoretic injection 

 through the microelectrode that this ionic diflusion is 

 satisfactorily explained by the hypothesis that the 

 inhiijitory synaptic transmitter increases the perme- 

 ability of the subsynaptic membrane to ions below a 

 critical size, e.g. to K+ and Cl~, and not to somewhat 

 larger ions, e.g. to Na+ (16; Grundfest, Chapter V, 

 fig. 12). This type of ionic mechanism appears to 

 occur with all types of central inhibition so far investi- 

 gated and also with the IPSP of the crustacean 

 stretch receptor cells (37, 60). It is remarkaljle that 

 a somewhat similar ionic mechanism explains the 

 vagal inhibitory action on the heart (25, 56, 76) and 

 probably for the inhibitory action on crustacean 

 muscle (42). 



The electrical diagram in figure 8C illustrates the 

 hypothesis that the inhibitory transmitter increases 

 the conductance of the subsynaptic membrane to 

 both K+ and Cl~ ions, which have the equilibrium 

 potentials indicated by the respective batteries, and 

 so cau.ses the flow of a current (fig. Bfi) which tends to 

 hyperpolarize the rest of the neuronal membrane to 

 about —80 mv, which is the mean of the equilibrium 

 potentials for K+ and Cl~ ions. 



Factors Controlling Impulse Generation 



The currents which flow from the subsynaptic 

 membrane to exert a hyperpolarizing action on the 

 motoneuronal membrane and .set up an IPSP (fig. 8 A, 

 inset) also effectively hyperpolarize the membrane of 

 the initial segment. However the currents generated 

 by this ionic mechanism are even more effective in 

 checking depolarization (18). On this account, with 

 any of the three methods of stimulation, synaptic, 

 direct or antidromic, there is an increased difficulty in 

 generating an impulse in the motoneuron. All the 

 various types of inhibitory action can be sufficiently 

 explained by the increased ionic conductance pro- 

 duced by the inhibitory transmitter substance and the 

 consequent flow of postsynaptic currents that oppo.se 

 the excitatory currents [fig. 8; cf Coombs et al. (18); 

 Eccles (29)]. 



The low threshold of the initial segment relative to 



the soma-dendritic membrane accounts for the ob- 

 servation that with normal motoneurons impulses are 

 always generated in the initial segment. As a conse- 

 quence the motoneuron acts as a far better integrator 

 of the whole synaptic e.xcitatory and inhibitory bom- 

 bardment than would be the case if impulses were 

 generated anywhere over the whole soma-dendritic 

 membrane. If these latter conditions obtained, a 

 special strategic grouping of excitatory synapses [cf 

 Lorente de No (65)] could initiate an impulse despite 

 a relative paucity of the total excitatory synaptic 

 bombardment and a considerable inhibitory bom- 

 bardment of areas remote from this focus. As it is, 

 both e.xcitatory and inhibitory synaptic action are 

 effective onlv in so far as they affect the membrane 

 potential of the initial segment. It is here that the 

 conflict between excitation and inhibition is joined, 

 not generally over the motoneuronal surface, as was 

 envisaged by Sherrington in his concept of algebraic 

 summation. 



In the account so far given the soma-dendritic 

 surface functions merely as a generating area for the 

 postsynaptic currents that are eff"ective only in so far 

 as they act on the initial segment either in generating 

 an impulse or in preventing it. If an impulse so 

 generated invades the soma-dendritic membrane, it 

 does so after the discharge has occurred along the 

 axon (14). It might thus appear that the invasion of 

 the soma-dendritic membrane is of no consequence in 

 the essential function of the neuron in discharging 

 impulses down its axon. However, in contrast to the 

 initial segment and the medullated axon of neurons, 

 the soma-dendritic membrane of many species of 

 neurons develops after an impulse a large and pro- 

 longed after-hyperpolarization (15, 68). This after- 

 hyperpolarization delays the generation of the next 

 impulse by the neuron and thus very eflTectively slows 

 the frequency of the rhythmic discharges of neurons 

 [cf Eccles (28), pp. 174-8]. This frequency control 

 by the soma-dendritic membrane is \ery important in 

 limiting the frequency with which motoneurons 

 activate muscles. Recently it has jjcen shown that the 

 motoneurons supplying the slow postural muscles ha\e 

 much more prolonged after-hyperpolarizations than 

 those supplying the fast phasic mu.scles (30). 



Central Inhibitory Patliivays 



It may be taken as established that at least some 

 afferent fibers, e.g. those from annulospiral endings 

 and tendon organs, act as pathways both for excita- 

 torv and inhibitory actions on motoneurons, and in 



