Skip to main content
Log in

Evidence for a GABAergic nigrothalamic pathway in the rat

I. Behavioural and biochemical studies

  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Summary

Unilateral stereotaxic microinjection of muscimol into the caudal region of the substantia nigra (SN) evoked tight, dose-related contralateral locomotor asymmetry and stereotypy. These behaviours were partially attenuated by various pre-treatments, including 6-hydroxydopamine lesions of the nigrostriatal dopamine pathway, intraperitoneal (i.p.) haloperidol, and inhibition of thalamic GABA-transaminase activity by local intrathalamic injection of ethanolamine-O-sulphate. Electrolytic or kainic acid lesions of the medial thalamic nuclei (MTN) partially reduced the contraversive rotation to intranigral muscimol, and completely abolished the similar behaviour elicited by apomorphine (25 μg) injected into the ipsilateral caudate nucleus. Contraversive turning to intranigral muscimol was completely inhibited by kainic acid lesions of the ipsilateral SN, but potentiated by intrathalamic injection of picrotoxin. Muscimol (40 ng-4 μg) administered to the MTN complex in one hemisphere stimulated rats to move in ipsilateral circles that were unaffected by haloperidol. The results of these behavioural experiments suggest that the nigrostriatal dopamine pathway, the nigrothalamic projection and possibly other non-dopaminergic SN efferents all play important roles in mediating the influences of the SN on motor and stereotyped behaviours. Disruption of the nigrothalamic pathway following electrical or chemical injury to the SN was accompanied by falls in GABA and its synthesising enzyme in the corresponding MTN. These data, together with the findings of our electrophysiological study presented in the following paper, are consistent with the nigrothalamic system having a GABAergic inhibitory function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Anderson M, Yoshida M (1977) Electrophysiological evidence for branching nigral projections to the thalamus and superior colliculus. Brain Res 137: 361–364

    Google Scholar 

  • Arnt J, Scheel-Krüger J (1979) GABAergic and glycinergic mechanisms within the substantia nigra: Pharmacological specificity of dopamine-independent contralateral turning behaviour and interactions with other neurotransmitters. Psychopharmacology 62: 267–277

    Google Scholar 

  • Balazs R, Machiyama Y, Hammond BJ, Julian T, Richter D (1970) The operation of the γ-aminobutyrate bypath of the tricarboxylic acid cycle in brain tissue in vitro. Biochem J 116: 445–467

    Google Scholar 

  • Bentivoglio M, Van Der Kooy D, Kuypers HGJM (1979) The organization of the efferent projections of the substantia nigra of the rat. A retrograde fluorescent double labelling study. Brain Res 174: 1–17

    Google Scholar 

  • Clavier RM, Atmadja S, Fibiger HC (1976) Nigrothalamic projections in the rat as demonstrated by orthograde and retrograde tracing techniques. Brain Res Bull 1: 379–384

    Google Scholar 

  • Costall B, Marsden CD, Naylor RJ, Pycock CJ (1976) The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling responses following 6-hydroxydopamine and electrolytic lesions of the ascending dopamine system of the brain. Brain Res 118: 87–113

    Google Scholar 

  • Dankova J, Boucher R, Poirier LJ (1975) Role of the striopallidal system and motor cortex in induced circus movements in rats and cats. Exp Neurol 47: 135–149

    Google Scholar 

  • Deniau JM, Hammond C, Riszk A, Feger J (1978) Electrophysiological properties of identified output neurons of the rat substantia nigra (pars compacta and pars reticulata): Evidences for the existence of branched neurons. Exp Brain Res 32: 402–422

    Google Scholar 

  • Di Chiara G, Olianas M, Del Fiacco M, Spano PF, Tagliamonte A (1977) Intranigral kainic acid is evidence that nigral non-dopaminergic neurones control posture. Nature (Lond) 268: 743–745

    Google Scholar 

  • Di Chiara G, Porceddu ML, Morelli M, Mulas ML, Gessa GL (1979) Evidence for a GABAergic projection from the substantia nigra to the ventromedial thalamus and to the superior colliculus of the rat. Brain Res 176: 273–284

    Google Scholar 

  • Domesick VB, Beckstead RM, Nauta WJH (1976) Some ascending and descending projections of the substantia nigra and ventral tegmental area in the rat. Neurosci Abstr 2: 61

    Google Scholar 

  • Faull RLM, Carman JB (1968) Ascending projections of the substantia nigra in the rat. J Comp Neurol 132: 73–92

    Google Scholar 

  • Faull RLM, Carman JB (1978) The cerebello-fugal projections in the brachium conjunctivum in the rat. I. The contralateral ascending pathway. J Comp Neurol 178: 495–518

    Google Scholar 

  • Faull RLM, Mehler WR (1978) The cells of origin of nigrotectal, nigrothalamic, and nigrostriatal projections in the rat. Neuroscience 3: 989–1002

    Google Scholar 

  • Fowler LJ, John RA (1972) Active-site-directed irreversible inhibition of rat brain 4-aminobutyrate aminotransferase by ethanolamine O-sulphate in vitro and in vivo. Biochem J 130: 569–573

    Google Scholar 

  • Garcia-Munoz M, Nicolaou NM, Tulloch IF, Wright AK, Arbuthnott GW (1977) Feedback loop or output pathway in striatonigral fibres? Nature (Lond) 265: 363–365

    Google Scholar 

  • Glowinski J, Iversen LL (1966) Regional studies of catecholamines in rat brain. 1. The disposition of [3H]norepinephrine, [3H]dopamine, and [3H]dopa in various regions of the brain. J Neurochem 13: 655–669

    Google Scholar 

  • Gottesfeld Z, Jacobowitz DM (1978) Neurochemical and anatomical studies of GABAergic neurons. In: Garattini S, Pujol JF, Samanin R (eds) Interactions between putative neurotransmitters in the brain. Raven Press, New York, pp 109–126

    Google Scholar 

  • Guyenet PG, Aghajanian GK (1978) Antidromic identification of dopaminergic and other output neurones of the rat substantia nigra. Brain Res 150: 69–84

    Google Scholar 

  • Herkenham M (1979) The afferent and efferent connections of the ventromedial thalamic nucleus in the rat. J Comp Neurol 183: 487–518

    Google Scholar 

  • James TA, Starr MS (1978) The role of GABA in the substantia nigra. Nature (Lond) 275: 229–230

    Google Scholar 

  • Jenner P, Leigh N, Marsden CD, Reavill C (1979) Dopamine mediated circling behaviour is modulated by lesions of the ventromedial nucleus of the thalamus. Br J Pharmacol 67: 432P-433P

    Google Scholar 

  • König JFR, Klippel RA (1963) The rat brain: A stereotaxic atlas of the forebrain and lower parts of the brain stem. Williams and Wilkins, Baltimore, MA

    Google Scholar 

  • Lowe IP, Robins E, Eyerman GS (1958) The fluorimetric measurement of glutamic decarboxylase and its distribution in brain. J Neurochem 3: 8–18

    Google Scholar 

  • MacLeod NK, James TA, Kilpatrick IC, Starr MS (1980) Evidence for a GABAergic nigrothalamic pathway in the rat. II. Electrophysiological studies. Exp Brain Res 40: 55–61

    Google Scholar 

  • Marshall JF, Ungerstedt U (1977) Supersensitivity to apomorphine following destruction of the ascending dopamine neurons: quantification using the rotational model. Eur J. Pharmacol 41: 361–367

    Google Scholar 

  • Martin GE, Papp NL, Bacino CB (1978) Contralateral turning evoked by the intranigral microinjection of muscimol and other GABA agonists. Brain Res 155: 297–312

    Google Scholar 

  • Olianas MC, De Montis GM, Concu A, Tagliamonte A, Di Chiara G (1978a) Intranigral kainic acid: Evidence for nigral non-dopaminergic neurons controlling posture and behaviour in a manner opposite to the dopaminergic ones. Eur J Pharmacol 49: 223–232

    Google Scholar 

  • Olianas MC, De Montis, GM, Mulas G, Tagliamonte A (1978b) The striatal dopaminergic functon is mediated by the inhibition of a nigral, nondopaminergic neuronal system via a strionigral GABAergic pathway. Eur J Pharmacol 49: 233–241

    Google Scholar 

  • Olpe HR, Schellenberg H, Koella WP (1977) Rotational behaviour induced in rats by intranigral application of GABA-related drugs and GABA-antagonists. Eur J Pharmacol 45: 291–294

    Google Scholar 

  • Reavill C, Jenner P, Leigh N, Marsden CD (1979) Turning behaviour induced by injection of muscimol or picrotoxin into the substantia nigra demonstrates dual GABA components. Neurosci Letters 12: 323–328

    Google Scholar 

  • Schwartz WJ, Gunn RH, Sharp FR, Evarts EV (1976) Unilateral electrolytic lesions of the substantia nigra cause contralateral circling in rats. Brain Res 105: 358–361

    Google Scholar 

  • Shellenberger MK, Gordon JH (1971) A rapid, simplified procedure simultaneous assay of norepinephrine, dopamine, and 5-hydroxytryptamine from discrete brain areas. Analyt Biochem 39: 356–372

    Google Scholar 

  • Snodgrass SR, Iversen LL (1973) A sensitive double isotope derivative assay to measure release of amino acids from brain in vitro. Nature (Lond) 241: 154–156

    Google Scholar 

  • Tulloch IF, Arbuthnott GW, Wright AK, Garcia-Munoz M, Nicolaou NM (1978) The striatonigral fibres and feedback control of dopamine metabolism. Psychol Med 8: 471–482

    Google Scholar 

  • Ueki A, Uno M, Anderson M, Yoshida M (1977) Monosynaptic inhibition of thalamic neurons produced by stimulation of the substantia nigra. Experientia 33: 1480–1482

    Google Scholar 

  • Ungerstedt U (1968) 6-Hydroxydopamine induced degeneration of central monoamine neurons. Eur J Pharmacol 5: 107–110

    Article  CAS  PubMed  Google Scholar 

  • Ungerstedt U (1971) Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behaviour. Acta Physiol Scand (Suppl 367) 82: 69–93

    Google Scholar 

  • Ungerstedt U, Arbuthnott GW (1970) Quantitative recording of rotational behaviour in rats after 6-hydroxydopamine lesions of the nigrostriatal dopamine system. Brain Res 24: 485–493

    Article  CAS  PubMed  Google Scholar 

  • Vincent SR, Hattori T, McGeer EG (1978) The nigrotectal projection: a biochemical and ultrastructural characterization. Brain Res 151: 159–164

    Google Scholar 

  • Wolfarth S, Dulska E, Golembioswka-Nikitin K, Vetulani J (1978) A role of the polysynaptic system of substantia nigra in the cholinergic-dopaminergic equilibrium in the central nervous system. Naunyn-Schmiedeberg's Arch Pharmacol 302: 123–131

    Google Scholar 

  • Wolfarth S, Dulska E, Harasiewicz A (1977) The participation of the nigro-thalamic pathway in the nigral control of the caudate nucleus; Pol J Pharm Pharmacol 29: 49–60

    Google Scholar 

  • York DH, Faber JE (1977) An Electrophysiological study of nigro-tectal relationships: A possible role in turning behaviour. Brain Res 130: 383–386

    Google Scholar 

  • Yoshida M, Omata S (1979) Blocking by picrotoxin of nigraevoked inhibition of neurons of ventromedial nucleus of the thalamus. Experientia 35: 794

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

This work was partly supported by an M.R.C. programme grant awarded to Prof. D.W. Straughan

I.C. Kilpatrick and A. Fletcher are respectively M.R.C. and S.R.C. scholars

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kilpatrick, I.C., Starr, M.S., Fletcher, A. et al. Evidence for a GABAergic nigrothalamic pathway in the rat. Exp Brain Res 40, 45–54 (1980). https://doi.org/10.1007/BF00236661

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00236661

Key words

Navigation