INHIBITORY TRANSMITTERS — A REVIEW 353 



to a postsynaptic cell would (1) increase the resting potential; (2) reduce or 

 abolish an i.p.s.p. ; and (3) reduce the size of an e.p.s.p. 



There are of course other conditions which must be met by any substance 

 which is postulated for the role of transmitter. These have often been sum- 

 marized, most recently perhaps by Florey (1960), and some are: (4) the sub- 

 stance must occur in detectable quantities in the neurons whose action it 

 transmits and must be synthesized there; (5) the postsynaptic structure should 

 contain an enzyme system for the inactivation of the transmitter; (6) during 

 stimulation of the neuron the substance should be detectable in the extra- 

 cellular fluid in the vicinity of the synapse, if necessary after inhibition of the 

 inactivating enzyme; and (7) drugs which potentiate or block the action of 

 the neuron should similarly affect the action of the apphed substance. 



Before considering to what extent known substances or extracts of unknown 

 constitution fulfil these various requirements, it should be noted that other 

 possibilities for depression of neuronal function exist. It will have been 

 noted that no mention has been made of blocking of the spike discharge of 

 the postsynaptic neuron. This of course will occur if sufficient aff"erent in- 

 hibitory influence of the type just described is brought to bear upon the cell 

 under observation, but it is possible also that such aboUtion of discharge 

 can occur from other causes. One such cause is the inhibition of a cell with 

 an associated reduction in amplitude of the e.p.s.p., but without the develop- 

 ment of an hyperpolarization resulting from inhibitory stimulation alone. 

 This phenomenon Frank and Fuortes (1959) have called "remote inhibition" 

 in contrast to the "direct" inhibitory process described above. Eccles (1961), 

 however, has shown that this inhibition is brought about by block of pre- 

 synaptic action as a consequence of excitation in adjacent neurons, and an 

 inhibitory transmitter is therefore not involved. Another possible cause of 

 inhibition of cell discharge is by the action of what may be called "depressor" 

 substances, whose eff'ect will be to reduce the excitability of the cell as a whole. 

 Such substances released into or artificiafly added to the extracellular ffuid 

 may prevent the discharge of a cell under study without having an eff'ect on 

 the resting potential. Both e.p.s.p.'s and i.p.s.p.'s evoked in a cell while under 

 the influence of such a depressor would be expected to be reduced in size. 



With these thoughts as background we will examine the qualifications of 

 various substances as possible inhibitory transmitters in the mammalian 

 central nervous system. In 1953, and in more detail in 1954, Florey reported 

 some of the actions of extracts of mammahan brain which had striking in- 

 hibitory properties on the slow-adapting neuron of the abdominal stretch 

 receptors of crayfish. These extracts were said to contain Factor I, and some 

 of their actions in Crustacea will be further considered below. Florey and 

 McLennan (1955a, b) studied the eff'ects of Factor I in the mammalian ner- 

 vous system and some of the pertinent observations may be presented here. 

 Factor I can be extracted from the central nervous system and from no other 



