Tetanus toxin and the synaptic release of GABA

Curtis, D. R.; Felix, Dominik; Game, C. J. A.; McCulloch, R.M.

doi:10.1016/0006-8993(73)90389-2

Cited by 132 publications

(44 citation statements)

References 12 publications

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“…This finding is in accord with other studies involving local toxin injections into different areas of the central nervous system (Brooks & Asanuma, 1965;Curtis et al 1973). Such factors as the rate of spread of the toxin in nervous tissue probably contributes significantly to the time of onset of action of the toxin.…”

Section: Discussionsupporting

confidence: 91%

“…However, it is not clear whether tetanus toxin has similar effects on supraspinal neurones to those reported on spinal neurones. Consistent with its actions on spinal inhibition tetanus toxin has been reported to interfere with the inhibitory effects of basket cells on cerebellar Purkinje neurones (Curtis et al 1973) and the recurrent inhibition of cerebral cortical neurones evoked by medullary stimulation (Brooks & Asanuma, 1965). Both these supraspinal inhibitions are sensitive to bicuculline and are therefore probably mediated by GABA (Curtis & Felix, 1971).…”

Section: Introductionmentioning

confidence: 91%

“…These proposals were based mainly on observations made on spinal neurones that tetanus toxin abolishes strychnine-sensitive and bicucullinesensitive synaptic inhibition by interfering with the release of the inhibitory neurotransmitter substances glycine or GABA from nerve terminals (Curtis & De Groat, 1968;Curtis, Felix, Game & McCulloch, 1973). However, it is not clear whether tetanus toxin has similar effects on supraspinal neurones to those reported on spinal neurones.…”

Section: Introductionmentioning

confidence: 99%

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

Davies¹,

Tongroach²

1979

The Journal of Physiology

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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.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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

Davies¹,

Tongroach²

1979

The Journal of Physiology

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“…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.…”

Section: Discussionmentioning

confidence: 59%

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

Mayer¹

1981

The Journal of Physiology

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Micro-injection of tetanus toxin (100-200 MLD) into the preoptic-anterior hypothalamus signficantly reduced the frequency ofoccurrence ofinhibition evoked from both sites.6. Pentobarbitone administered acutely or as the sole anaesthetic increased both the duration and frequency of occurrence of inhibitory responses evoked from the arcuate-ventromedial nuclei.7. It is suggested that a GABA-linked inhibitory synaptic mechanism, activated by arcuate-ventromedial and periaqueductal grey stimulation, operates in the preoptic-anterior hypothalamus. Such convergent inhibition may be a result of activity in local interneurone circuitry.

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“…Diazepam (3.0mgkg-', i.p., given I h before and after the toxin injection and once a day for 4 or 7 days after) did not show any protective effect against the neuropathological ( toxicity to be achieved. This idea is also supported by electrophysiological evidence indicating that tetanus toxin blocks inhibitory transmission (mainly GABAergic) at the presynaptic level, leaving unaffected the excitatory input within the CNS (Curtis & De Groat, 1968;Curtis et al, 1973;Davies & Tongroach, 1977;Calabresi et al, 1989) and in foetal mice dissociated spinal cord neurones (Bergey et al, 1987). The doses of tetanus toxin used in our experiments were smaller than that (104 LD5O) producing 40% inhibition of K+-evoked GABA release in hippocampal slices (Collingridge et al, 1981) but similar to those used for producing an excitatory focus in the same region De Sarro et al, 1985).…”

Section: Antagonism Studymentioning

confidence: 77%

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

Bagetta

Nisticò

Bowery

1990

British J Pharmacology

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The behavioural and neuropathological effects of tetanus toxin, microinjected directly into the hippocampus, were studied in rats. A single dose (1000 minimum lethal doses, MLDs) of tetanus toxin, injected unilaterally into the hippocampus produced a time‐dependent neuronal loss in the CA1 pyramidal cell layer. In comparison with the contralateral, untreated side these effects became statistically significant (P > 0.05) 7 days (22.0 ± 1.1% reduction) and 10 days (29.2 ± 1.7% reduction) after the injection. No significant changes were observed 7 days after treatment with 500 MLDs whereas a reduction of 37.5 ± 3.1% in the CA1 area cell number was produced 4 days after the injection of 2000 MLDs. Behavioural stimulatory effects were also induced by tetanus toxin (1000 MLDs) within 48 h of the injection and these culminated in generalized convulsions 5–7 days later. Convulsions were observed after a shorter period of latency in rats receiving 2000 MLDs tetanus toxin whereas 500 MLDs were ineffective. No behavioural and neuropathological effects were observed in rats treated with neutralized tetanus toxin (1000 MLDs), bovine serum albumin or phosphate buffer. Pretreatment with MK801 (0.3 mg kg−1, i.p., given 1 h before and after the injection with tetanus toxin and then once daily for 4 or 7 days) prevented the behavioural and neuropathological effects induced by tetanus toxin (1000–2000 MLDs). In addition, such treatment fully protected the animals from the lethal effects induced by 1000 MLDs tetanus toxin. By contrast, pretreatment with diazepam (3.0 mg kg−1, i.p.) using the same schedule as for MK801 did not antagonize the effects of tetanus toxin (1000–2000 MLDs). In conclusion, the present experiments have demonstrated that the intrahippocampal injection of tetanus toxin produces in rats a dose‐ and time‐dependent behavioural stimulation and neuronal loss in the CA1 pyramidal cell layer which can be prevented by the non‐competitive NMDA antagonist, MK801.

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Tetanus toxin and the synaptic release of GABA

Cited by 132 publications

References 12 publications

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

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

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

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

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