Amino acid transmitters in the mammalian central nervous system

126 D.R. CURTIS and G.A.R. JOHNSTON :
sion of feline cortical neurones by glycine (CURTIS et al., 1968 a, 1971 b; JOHNSON
et al., 1970), fl-alanine and taurine (CURTIS et al., 1968a, 1971b), the action
of GABA being relatively insensitive. The same high degree of selectivity appears
not to occur when rat cortical neurones were studied (BISCOE et al., 1972). Furthermore
the inhibition of the firing of pyramidal tract cells in the cat by local
cortical stimulation (KRNJEVI~;, RANDIC and STRAUGHAN, 1966; CRAWFORD,
CURTIS, VOORHOEVE, and WILSON, 1963), by recurrent volleys in the pyramidal
tract (CRAWFORD et al., 1963 ; BISCOE and CURTIS, 1967), by stimulation of thalamic
nuclei (KRNJEVIC; et al., 1966), and by direct chemical stimulation of intracortical
interneurones (BISCOE and CURTIS, 1967) was not blocked by strychnine.
In contrast, electrophoretically administered bicuculline selectively reduced
the inhibitory effect of GABA and some related amino acids (fl-alanine, taurine
and imidazole acetic acid) on cortical neurones of the cat (CURTIS et al., 1971 b;
see also STRAUGHAN, NEAL, SIMMONDS, COLLINS, and HILL, 1971). Similar
results have been observed using bicuculline methochloride (CURTIS, GAME, JOHN-
SXON, and MCCULLOCH, unpublished observations). The same degree of selectivity
has not been demonstrated in the rat cortex (BISCOE et al., 1972) where in a
high proportion of tests bicuculline reduced the effects of both glycine and GABA.
These observations are of considerable relevance to the reduction by bicuculline
of the synaptic inhibition of pyramidal tract neurones by recurrent volleys, direct
cortical electrical stimulation or chemical excitation of intracortical neurones
(Cat: CURTIS and FELIX, 1971). Additionally, antagonism of the inhibitory effects
of fl-alanine and taurine on cortical neurones by both strychnine and bicuculline
probably excludes either amino acid as a transmitter of inhibitory synapses selectively
blocked by bicuculline.
Picrotoxin has also been reported to reduce the inhibition of cortical neurones
in the cat by GABA (HILL, NIMMONDS, and STRAUGHAN, 1972b), and to reduce
the effects of both GABA and glycine in the rat cortex (BISCOE et al., f972).
Further investigation is warranted since the recurrent inhibition of pyramidal
cells in the cat has been reported to be diminished by relatively low doses (0.1-
0.3 mg/kg, BROOKS and ASANUMA, 1965), but inhibition evoked by direct cortical
stimulation appeared insensitive (0.6-2 mg/kg, KRNJEVI{~ et al., 1966). This latter
inhibition was also apparently not modified by tetanus toxin (KRNJEVI~ et al.,
1966), although abolition of the recurrent and transcallosal inhibition of pericruciate
neurones (BROOKS and ASANUMA, 1965) suggests that the effects of tetanus
toxin may be similar to those found in the cerebellar cortex (CURTIS et al.,
1973 a). Penicillin has also been demonstrated to antagonize the inhibitory effect
of GABA on cortical neurones, an action which may account for the epileptogenic
activity of this compound (CURTIS et al., 1972b).
As a consequence of these studies, a proportion of stellate cells in the cerebral
cortex may be considered inhibitory in nature, releasing GABA at axosomatic
synapses on pyramidal cells (see CURTIS and FELIX, 1971). Further studies are
required to ascertain the location of the interneurones activated by volleys in
particular inhibitory pathways, and to determine the significance of the inhibitory
control by this amino acid in the functioning of pyramidal and stellate cells
in various cortical areas. The importance of glycine as a cortical transmitter
may be minimal, the effects of strychnine on cortical activity (AJMONE-MARSAN,