Amino acid transmitters in the mammalian central nervous system

Amino Acid Transmitters in the Mammalian Central Nervous System 161
The effects of tetanus toxin on spinal inhibitions are relevant to the role
of GABA as an inhibitory transmitter since the toxin suppresses GABA-mediated
inhibition in the cerebellum (Section 4.2.2). Following intramuscular (SVERDLOV
and ALEKSEEVA, 1965 ; SVFRDLOV and KOZHECNKIN, 1969) or intraspinal (CURTIS
et al., 1973 a) administration, short latency glycine-mediated inhibitions of motoneurones
are diminished, and subsequently there is a reduction in prolonged
inhibitions accompanied by reduced PAD (CURTIS et al., 1973 a). Since Renshaw
cells affected by the toxin remain sensitive to GABA (CURxIS and DE GROAT,
1968), and spinal levels of GABA are unaffected (JOHNSTON et al., 1969; SEMBA
and KANO, 1969; FEDINEC and SHANK, 1971), the toxin presumably interferes
with the synaptic release of GABA, an action similar to that occurring at glycinereleasing
terminals. The differences in the latency of the action of this toxin
on the two types of spinal inhibition may be related to the predominantly somatic
location of glycine releasing terminals and the probable association of GABA
with axodendritic inhibitory synapses.
Several processes thus appear responsible for the long latency and prolonged
inhibition of spinal motoneurones by afferent volleys in segmental afferents and
from higher centres (Sc~MIDT, 1971). The central effects of these volleys are
complex, both presynaptic and postsynaptic factors may be involved, but the
release of GABA from the terminals of a particular type of inhibitory interneurone
appears to be essential to the prolonged inhibitory process. To what extent
this type of inhibition normally regulates the activity of spinal neurones other
than motoneurones remains to be elucidated, as does the location and characterization
of the interneurones and their synaptic interconnections with different
types of afferent fibre, fibres from supraspinal regions and the axons of other
spinal interneurones. Neurochemical evidence suggests that most of these GABA
releasing interneurones, or their synaptic endings, are located in the dorsal horn.
Other features requiring further investigation are the prolonged time course of
this type of inhibition and its enhancement by anaesthetics and other agents
(ScHMIDT, 1971), an effect which may be common to other synapses operated
by GABA where transmitter action is similarly of long duration (NICOLL, 1972).
4.13. Non-Central Neurones
Although possibly not strictly relevant to the central theme of this review, the
effects of amino acids upon dorsal root sensory ganglia and autonomic ganglia
are of considerable interest, and may be of significance in relation to transmitter
functions of amino acids.
4.13.1. Dorsal Root Ganglia
Analyses of lumbar dorsal ganglia indicate relatively high intraganglionic levels
of a number of amino acids, including aspartate, glutamate and glycine (Table 8),
but extremely low levels of GABA (< 0.06 gmole/g, concentration approx.
0.2 mM, Cat: OTSUKA et al., 1971. Rat: 0.3 gmole/g, GOTa'ESFELD, KELLY, and