Amino acid transmitters in the mammalian central nervous system

146 D.R. CURTIS and G. A. R. JOHNSTON :
SCHWARTZ, 1967, 1968), the effect of D-glutamate being somewhat weaker
(GALINDO et al., 1967). Although both the excitatory actions of L-glutamate,
L-aspartate and the synaptic firing of cuneate neurones were reduced by 1-hydroxy-3-aminopyrrolidone-2,
supporting an excitatory transmitter function for the
amino acid (Cat: DAVIES and WATKINS, 1973), the specificity of the antagonist
towards other excitants of these neurones has not been determined. When administered
topically to these nuclei L-aspartate (10-2 M) was apparently without effect
whereas, L-glutamate (10- 4-10 2 M) depolarized terminals of afferent fibres (Rat:
DAVIDSON and SOVTHWICK, 1971). Since this effect was not observed after the
administration of sufficient picrotoxin to suppress the depolarization of terminals
by conditioning volleys in afferent fibres, the depolarization of by L-glutamate
has been considered to be unrelated to "presynaptic" inhibition in the cuneate
nucleus (DAVIDSON and SOUTHWICK, 1971).
4.11.2. Inhibition
Although the levels of individual amino acids in the gracile and cuneate nuclei
have not been determined, both glycine and GABA have been considered as
possible inhibitory transmitters. When administered electrophoretically these
amino acids depress the activity of cuneate neurones; in general glycine is as
effective as GABA although proprioceptive cells appear more sensitive to the
latter amino acid (Cat: GALINOO et al., 1967). The effect ofglycine can be blocked
by strychnine, that of GABA by picrotoxin (Cat: GALINOO, 1969) or bicuculline
(Cat: KELLY and RENAUD, 1971).
A number of studies have been concerned with the effects of amino acids
on the excitability of cuneate presynaptic terminals, particularly in relation to
the possible role of GABA in "presynaptic" inhibition. Although both glycine
and GABA (electrophoretic) have been shown to diminish the excitability of
the terminals of primary afferent fibres within the cuneate nucleus (GALINDO,
1969), the effect of GABA being blocked by electrophoretic picrotoxin, most
experiments have involved topical administration of amino acid solutions. Under
these conditions glycine (10- 2 M) reduced (Rat: DAVIDSON and SOUTHWICK,
1971), whereas GABA (10 -4 10 1M) enhanced presynaptic excitability (Cat:
GALINDO, 1969. Rat: DAVIDSON and SOUTHWICK, 1971). This effect of GABA
was blocked by picrotoxin (GALINDO, t969); alternatively topical GABA
blocked the suppression by picrotoxin of primary afferent depolarization (PAD)
induced by afferent volleys (DAvIDSON and SOUTHWlCK, 1971).
Both short (20 msec) and long (about 200 msec) duration postsynaptic inhibition,
and prolonged "presynaptic" inhibition have been proposed to account
for the depression of transmission through the cuneate nucleus which follows
cutaneous afferent volleys (ANDERSEN, ECCLES, OSHIMA, and SCHMIDT, 1964;
ANOERSEN, ETr~OLM, and GORDON, 1970). "Presynaptic" inhibition has frequently
been assessed by the presence of afferent terminal depolarization, and the
involvement of GABA in these inhibitory processes is suggested by the
following findings: semicarbazide lowered central GABA levels and reduced
afferent terminal depolarization (Cat: BANNA and JABBUR, 1971); afferent