Tetanus toxin and synaptic inhibition in the substantia nigra and striatum of the rat.

Abstract

SUMMARY1. The effects of tetanus toxin were determined on GABA-mediated synaptic inhibition of substantia nigra neurones evoked by striatal stimulation and on the presumed dopamine-and 5-hydroxytryptamine-mediated synaptic inhibition of striatal neurones evoked by nigral and dorsal raphe nucleus stimulation, respectively, in the urethane-anaesthetized rat.2. Following an intranigral injection of tetanus toxin, striatal-evoked inhibition of substantia nigra neurones, which is sensitive to bicuculline, was rapidly abolished. This effect was not accompanied by any significant change in the responses of nigral neurones to ionophoretically administered GABA or other putative neurotransmitters and thus indicates a presynaptic site of action of the toxin. 3. The rate of onset of action of the toxin in the substantia nigra was extremely rapid (1-4 min) and appeared to be related to the rate of activation of the inhibitory pathway.4. Injections into the substantia nigra of tetanus toxin neutralized with antitoxin had no significant effect on striatal-evoked inhibition in the substantia nigra.5. Injections of tetanus toxin into the striatum failed to influence the inhibition of striatal neurones evoked by stimulation of the ipsilateral substantia nigra or the dorsal raphe nucleus, suggesting that tetanus toxin does not impair monoaminemediated inhibition in the central nervous system. 6. Synaptic excitation which preceded substantia-nigra-evoked inhibition in striatal neurones and which occasionally preceded striatal-evoked inhibition in nigral neurones was also unaffected by tetanus toxin.7. It is suggested that tetanus toxin selectively abolishes GABA-mediated synaptic inhibition in the central nervous system and may be a useful tool in the identification of such synaptic inhibitory mechanisms.

Electrophysiological analysis of inhibitory synaptic mechanisms in the preoptic area of the rat.

“…Tetanus toxin is considered to act by preventing the synaptic release of inhibitory amino acids (Osborne & Bradford, 1973;Curtis, 1971), and has been shown to abolish synaptic inhibition believed to be mediated by these amino acids at both spinal and supra-spinal sites (Curtis & de Groat, 1968;Curtis, Felix, Game & McCulloch, 1973; PREOPTIC AREA INHIBITORY MECHANISMS Davies & Tongroach, 1979). Reduction of the frequency of occurrence of synaptic inhibition in the preoptic-anterior hypothalamus by tetanus toxin provides valuable confirmatory evidence in support of the earlier suggestion that such inhibition is mediated by amino acid transmitters.…”

Effect of tetanus toxin on the excitatory and the inhibitory post‐synaptic potentials in the cat motoneurone.

“…Since then it has been shown that many kinds of inhibitory synapses in the central nervous system (c.N.s.) are blocked by tetanus toxin (Brooks & Asanuma, 1962;Curtis & De Groat, 1968;Curtis, Felix, Game & McCulloch, 1973; Davies & Tongroach, 1979) while some excitatory synapses in the spinal cord and the substantia nigra are not affected (Brooks et al 1957;Geinisman,' D'yakonova & Kryzhanovsky, 1967;Curtis & De Groat, 1968; Kryzhanovsky, Kurchavyi & Sheikhon, 1973;Takano, 1976; Davies & Tongroach, 1979). Therefore, it has been generally considered that tetanus toxin does not act directly on excitatory synapses in the C.N.s.…”

Prevention by the NMDA receptor antagonist, MK801 of neuronal loss produced by tetanus toxin in the rat hippocampus

“…However, excitation and perhaps degeneration could also arise without any net change in glutamate levels if the GABAmediated inhibitory input is reduced. We have tested this hypothesis using tetanus toxin which selectively blocks the GABAergic inhibitory tone in the CNS (Davies & Tongroach, 1979) and the release of GABA in rat hippocampal slices (Collingridge et al, 1981 (coordinates A = -4mm from the bregma, L = 2 mm from the midline, V = 2.4 mm below the dura mater according to the rat brain atlas of Paxinos & Watson, 1982; the volume of injection was 1l 4umin-1) by means of a Hamilton microsyringe (5 pl) mounted on a stereotaxic frame. Animals injected with bovine serum albumin (BSA), phosphate buffer (pH = 7.0; used to dissolve tetanus toxin) and neutralized tetanus toxin (the neutralization was carried out with a F(ab)' fragment of the native IgG antitetanus toxin as previously described by Gawade et al, 1985) were used as controls.…”