Amino acid transmitters in the mammalian central nervous system

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144 D.R. CURTIS and G.A.R. JOHNSTON : 1973), glycine usually being more effective than GABA when the amino acids are administered near cell bodies, with a reverse order of relative potency when the amino acids were administered more dorsally near dendrites (Rabbit: ALa'- MANN, BRUGGENCATE, and SONNHOF, 1972). Both of these amino acids, and flalanine and b-aminovaleric acid, increase the membrane conductance of hypoglossal motoneurones and hyperpolarize these cells (BRUGGENCATE and SONNHOF, 1972). Furthermore the inhibitory effect of glycine is selectively blocked by strychnine (Cat: BRUGGENCATE and NONNHOF, 1972. Rat: DUGGAN et a1.,1973) and that of GABA by picrotoxin (BRUGGENCATE and SONNHOF, 1972) and bicuculline (DUGGAN et al., 1973). Since IPSP's recorded from hypoglossal motoneurones in response to impulses in the lingual nerve are reduced by strychnine (Cat: Intravenous 0.08 mg/kg, MORIMOTO, TAKATA, and KAWAMURA, 1968), and inhibition evoked by impulses in the glossopharyngeal nerve, and associated with chloride sensitive IPSP's, can be reduced by intravenous or electrophoretic strychnine but not by electrophoretic bicuculline (Rat: DUGGAN et al., 1973), glycine can be assumed to be an inhibitory transmitter influencing hypoglossal motoneurones most probably at axosomatic synapses. The relatively higher sensitivity of the dendritic regions of these cells to GABA may be associated with an inhibitory transmitter function of this amino acid at axodendritic synapses (see ALTMANN et al., 1972). It is thus significant that impulses in high threshold hypoglossal afferents have been reported to produce long latency and duration chloridesensitive IPSP's in hypoglossal motoneurones, an inhibitory effect blocked by picrotoxin (2mg/kg) but not by strychnine (0.2ms/ks, Cat: MORIMOTO and KAWAMURA, 1972). 4.10.2. Reticular Formation In the brain stem and medullary reticular formation most investigations have been concerned with anatomically located "reticular" neurones, although the sensitivity of antidromically identified reticulospinal neurones to depressant amino acids has been correlated with the operation of certain inhibitory pathways. Medullary reticulospinal neurones are approximately equally sensitive to L- glutamate and L-aspartate (Cat: TEB~:ClS, 1973b)as are reticular neurones (Cat: H/SSLI and TEB~CIS, 1970). In both of these studies DL-homocysteate was a more potent excitant than either naturally occurring acidic amino acid, although another report suggests that unlike the situation elsewhere in the nervous system, medullary reticular neurones excited by DL-homocysteate were not always excited by L-glutamate, and vice versa (Cat: BOAKES et al., 1970). Lysergic acid diethylamide (LSD) has been reported to block the excitation of medullary reticular neurones by 5-hydroxytryptamine and L-glutamate, the excitatory action of acetylcholine, DL-homocysteate, noradrenaline and of L- glutamate on cells depressed by 5-hydroxytryptamine, being unaffected (Cat: BOAKES et al., 1970). In contrast, in the rat, LSD reduced the effect of L-glutamate on neurones within the dorsal and median raph6 nuclei which were depressed by 5-hydroxytryptamine (Rat: AGHAJANIAN, HAIGLER, and BLOOM, 1972).
Amino Acid Transmitters in the Mammalian Central Nervous System 145 Of the depressant amino acids, glycine was usually more effective than GABA in reducing the firing rate of reticular (H6sLI and TEBEClS, 1970) and reticulospinal (TEB~CIS and DI MARIA, 1972 b) neurones in the cat. When administered extracellulary glycine increased the membrane conductance of reticular neurones, producing a chloride sensitive hyperpolarization: reticular neurones (HOsLI, TEBF.CIS, and HAAS, 1971 ; H6SLI and HAAS, 1972); reticulospinal neurones (TEB~;ClS and ISHIKA- WA, 1973). The latter cells are also hyperpolarized by GABA. The inhibitory effect of glycine (and of fl-alanine) is readily reduced by strychnine which shows little antagonism towards GABA (H6sLI and TEB~CIS, 1970; TEB~CIS and DI MARIA, 1972). On the other hand selective antagonism of either amino acid has not been demonstrated using picrotoxin (Electrophoretic, intravenous, Cat: H6SLI and TEB~ClS, 1970) and both bicuculline (reticular neurones, TEB~ClS, H6SLI, and HAAS, 1971) and bicuculline methochloride (reticulospinal neurones, TEBEClS, 1973b) reduced the depressant action of glycine and GABA, although the effect of glycine was usually less sensitive to these alkaloids than that of GABA. The selectivity of bicuculline towards GABA receptors on reticular neurones is thus less than that demonstrated in the spinal cord. The relatively weak inhibitory effect of imidazole-4-acetate on reticular neurones was not affected by strychnine, but was reduced by bicuculline (HAAS et al., 1972). Furthermore strychnine, but not bicuculline, selectively blocked the inhibitory effect of taurine on medullary reticular neurones (HAAS and H6SLI, 1973 a). On the basis of the effects of strychnine on the inhibition of medulary reticulospinal neurones by stimulation of reticulospinal axons (and presumably mediated via axon collaterals: ITO, UDO, and MAYO, 1970) glycine has been proposed as an inhibitory transmitter released by one type of neurone in the ventrocaudal portion of the medial medullary reticular formation (TEBECIS and DIMARIA, 1972; TEBECIS and ISHIKAWA, 1973). A strychnine sensitive inhibition of reticulospinal neurones could also be evoked by stimulation in the medial pontine reticular formation (TEBF.CIS and DI MARIA, 1972). These types of relatively short latency and duration inhibition were usually insensitive to bicuculline (but see TEB~CIS, 1973b) and some evidence has also been provided for a picrotoxin-sensitive (2 mg/kg intravenous) long duration inhibition of reticulospinal neurones, evoked by ventral spinal cord stimulation, which may involve GABA (Cat: TEBECIS and ISHIKAWA, 1973). Strychnine also suppressed the inhibition of medullary reticular neurones by impulses in limb nerves (HAAS and HOSLI, 1973 b), 4.11. Dorsal Column Nuclei 4.11.1. Excitation In the cat, glutamate levels within the dorsal medullary region containing primary sensory nuclei are significantly higher (6.93 +0.53 ~tmole/g) tkan those of the ventral medulia (5.94+ 0.30, JOHNSON and APRISON, 1970), findings consistent with the high levels of this amino acid in dorsal roots and columns. Neurones of the gracile and cuneate nuclei are readily excited by L-glutamate (Cat: MEYER, 1965; STEINER and MEYER, 1966; GALINDO, KRNJEVIC, and
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Amino acid transmitters in the mammalian central nervous system

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