122 D.R. CURTIS and G. A. R. JOHNSTON : depolarization of cortical neurones by L-glutamate (KRNJEVIC, 1964) is associated with an <strong>in</strong>creased membrane conductance (KRNJEVIC and SCHWARTZ, 1967a). As elsewhere <strong>in</strong> <strong>the</strong> fel<strong>in</strong>e CNS, <strong>the</strong> effects of electrophoretic glutamate and aspartate are characteristically rapid <strong>in</strong> both onset and recovery, <strong>the</strong> potencies of <strong>the</strong> L-isomers are similar and only slightly greater than those of <strong>the</strong> D-isomers. No <strong>system</strong>atic variations have been found <strong>in</strong> <strong>the</strong> relative sensitivity of different cortical neurones to glutamate, aspartate and DL-homocysteate (CRAWFORD, 1970), although such a study should be repeated with anatomical/physiological identification of cell types. Surface stimulation of <strong>the</strong> cruciate cortex <strong>in</strong>hibits <strong>the</strong> fir<strong>in</strong>g of pyramidal cells excited by L-glutamate for much longer periods than fir<strong>in</strong>g at <strong>the</strong> same frequency produced by DL-homocysteate (MCLENNAN, 1970). Although this may <strong>in</strong>dicate differences <strong>in</strong> <strong>the</strong> nature of L-glutamate and DL-homocysteate receptors (MCLENNAN, 1970), an alternative explanation has been provided <strong>in</strong> terms of <strong>the</strong> distribution of am<strong>in</strong>o <strong>acid</strong> receptors activated by <strong>the</strong>se excitants (CURTIS et al., 1972a). A number of possible antagonists of am<strong>in</strong>o <strong>acid</strong> excitation have been tested <strong>in</strong> <strong>the</strong> fel<strong>in</strong>e pericruciate cortex, particularly on cells also fired by acetylchol<strong>in</strong>e. Selective antagonism of excitation by aspartate and glutamate (and DL-homocysteate) has been demonstrated us<strong>in</strong>g L-methion<strong>in</strong>e-DL-sulphoxim<strong>in</strong>e, 2-methoxyaporph<strong>in</strong>e (CURTIS et al., 1972a) and 1-hydroxy-3-am<strong>in</strong>opyrrolidone-2 (DAVIES and WATKINS, 1972, 1973). None of <strong>the</strong>se agents appeared to modify <strong>the</strong> spontaneous fir<strong>in</strong>g of cortical neurones, and <strong>the</strong> effects on synaptic fir<strong>in</strong>g have yet to be determ<strong>in</strong>ed. 4.1.2. Inhibition The extensive literature concern<strong>in</strong>g <strong>the</strong> possible role of neutral am<strong>in</strong>o <strong>acid</strong>s, particularly GABA, as <strong>in</strong>hibitory <strong>transmitters</strong> <strong>in</strong> <strong>the</strong> <strong>mammalian</strong> cerebral cortex has been <strong>the</strong> subject of numerous reviews (ROBERTS, 1960, 1968; CURTIS and WATKrNS, 1965 ; KRNJEVId, 197b ; SYTINSKY, 1972). The essential evidence can be summarized as follows. Cortical glyc<strong>in</strong>e levels are relatively low (Table 3) and <strong>the</strong> content <strong>in</strong> <strong>the</strong> cerebral hemispheres of <strong>the</strong> cat (1.3 gmole/g) and rat (0.8-1 ~tmole/g) are lower than those of sp<strong>in</strong>al grey matter (SHAw and HEINE, 1965; APRISON, SHANK, and DAVIDOFF, 1969; see also SHANK and APRISON, 1970). A high aff<strong>in</strong>ity uptake <strong>system</strong> for glyc<strong>in</strong>e has not been found <strong>in</strong> cortical tissue (Rat: JOHNSTON and IVERSEN, 1971 ; NEAL, 1971 ; BENNETT et al., 1972). There are considerable species differences <strong>in</strong> cortical levels of taur<strong>in</strong>e (Table 3; see also GAITONDE, 1970). High levels are found <strong>in</strong> <strong>the</strong> cerebral hemispheres of <strong>the</strong> rat (%8 p.mole/g, KACZMAREK, AGRAWAL, and DAVISON, 1971; SHANK and APRISON, 1970) and <strong>the</strong> mouse (VAN GELDER, 1972) although levels <strong>in</strong> <strong>the</strong> cerebral cortex of <strong>the</strong> cat are lower. No particular association with synaptosomes has been demonstrated. There seems to be little correlation between regional distributions of taur<strong>in</strong>e and <strong>the</strong> enzyme responsible for its syn<strong>the</strong>sis although cyste<strong>in</strong>e sulph<strong>in</strong>ic <strong>acid</strong> decarboxylase is present <strong>in</strong> synaptosomes (KACZMAREK, AGRAWAL, and DAVISON, 1970). Two uptake <strong>system</strong>s for taur<strong>in</strong>e have been demon-
<strong>Am<strong>in</strong>o</strong> Acid Transmitters <strong>in</strong> <strong>the</strong> Mammalian Central Nervous System 123 ,~o