Amino acid transmitters in the mammalian central nervous system

Amino Acid Transmitters in the Mammalian Central Nervous System 139
disease, and may indicate the involvement of GABA in a pallidal-nigral inhibitory
pathway (MCGEER et al., 1971). In the presence of amino-oxyacetic
acid, slices of rat substantia nigra accumulate GABA to a greater extent than
either glycine or leucine (OKADA and HASSLER, 1973).
Cells of the feline substantia nigra are excited by electrophoretic glutamate
and aspartate, and firing is inhibited by GABA, the cells being relatively insensitive
to glycine (FELTZ, 1971). Inhibitory hyperpolarizing potentials have been recorded
from nigral neurones after stimulation within the caudate nucleus, the long latency
IPSP's (14.6-20 msec) being considered monosynaptic with a conduction velocity
of the afferent fibres approximating 0.9 ms- t (Cat: YOSHIDA and PRECHT, 1971).
The finding that the accompanying positive extracellular field potentials and
the inhibition of spontaneously active neurones were reduced by intravenous
picrotoxin (2.5 mg/kg), but not by strychnine (0.6 mg/kg), (PRECHT and YOSHIDA,
1971) supports the participation of GABA as the inhibitory transmitter of this
caudato-nigral pathway.
4.8.2. Caudate and Other Nuclei
Table 7 indicates that in a number of species GABA levels are moderate in
the caudate and putamen and higher in the globus pallidus. These figures are
consistent with the levels of GAD in the caudate (16.2 gmole GABA/g dry weight/
hour, putamen 16.4, and globus pallidus 33.4, Monkey: LOWE et al., 1958).
Similarly high enzyme levels have been reported in the human (MrOLLER and
LANGEMANN, 1962; MCGEER et al., 1971). In contrast, however, the levels of
GABA-T are relatively low in the monkey globus pallidus, but higher in the
putamen and caudate (SALVADOR and ALBERS, 1959). High levels of GABA-T
have been found in the human basal ganglia (SHERIDAN, SIMS, and PITTS, 1967).
The caudate content of other amino acids is listed'by DEFEUDIS et al., (1970),
PERRY et al., (1971 a, b, 1972) and SHIMADA et al., (1972). The uptake of GABA,
aspartate and glutamate by subcellular particles of the rat striatum has been
studied by GFELLER, KUHAR, and SNYDER (1971).
Striatal GABA levels in the rat are not altered by transection of nigrostriatal
pathways (KIM et al., 1971), and the GAD content of the cat
caudate is not altered after mid-brain lesions in the vicinity of the substantia
nigra (HOCKMAN, LLOYD, FARLEY, and HORNYKIEWICZ, 1971). Apart from these
observations no information is avai.lable regarding the possible origin of GABA
releasing inhibitory pathway projecting to these basal ganglia nuclei, although
if caudato-pallidal fibres are axon collaterals of the inhibitory caudato-nigral
pathway, GABA may be involved as an inhibitory transmitter within the pallidum
as well as in the substantia nigra (see YOSHIDA, RABIN, and ANDERSON, 1972).
Caudate neurones are readily excited by L-glutamate or DL-homocysteate
(Cat: BLOOM, COSTA, and SALMOIRAGm, 1965; MCLENNAN and YORK, 1967;
CONNOR, 1970. Rabbit: HERZ and YON FREYTAG-LORINGHOVEN, 1968) and
depressed by GABA (BLooM et al., 1965 ; HERZ and VON FREYTAG-LORINGHOVEN,
1968). The excitant amino acids are also effective in the globus pallidus-putamen
(Cat:YORK, 1968. Monkey: YORK, 1972).