Skip to main content
SpringerLink
Log in

Reduction of apomorphine-induced rotational behaviour by subthalamic lesion in 6-OHDA lesioned rats is associated with a normalization of firing rate and discharge pattern of pars reticulata neurons

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

The effect of subthalamic nucleus (STh) lesion on apomorphine-induced rotational behaviour and unit activity of substantia nigra pars reticulata (SNr) neurons was studied in normal, sham-control and unilateral 6-OHDA-lesioned rats [SN pars compacta (SNc)-lesioned]. In the latter, contraversive rotational behaviour was greatly reduced by an additional ipsilateral STh lesion. A moderate ipsiversive rotation was observed in rats with a single STh lesion. Concurrently, SN unit extracellular recordings were performed in age-matched normal rats, sham-controls for both lesions, STh-lesioned rats, SNc-lesioned rats, and SNc-lesioned rats with an ipsilateral STh lesion (SNc+STh-lesioned). Pars reticulata neurons had a higher mean firing rate in SNc-lesioned rats than in control rats. Furthermore, 68% of SNr neurons in SNc-lesioned rats had a tonic discharge pattern (against 92.3% in control rats) and 32% a mixed or bursting pattern. After STh lesion, a clear decrease in SNr firing rate was observed in SNc-lesioned rats. Moreover, STh lesion improved interspike interval regularity and decreased the occurrence of bursting patterns. In rats with a single STh lesion, the firing rate was no different from that of the sham-controls but the discharge pattern was more regular. These data show that STh lesion decreased apomorphine-induced rotational behaviour in dopamine-depleted animals. This effect could be related to the suppression of the exitatory effect of STh efferents on the SNr neurons. STh lesion both counterbalanced the increased activity of SNr neurons and regularized their discharge pattern.

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

Access this article

Log in via an institution

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

  • Aghajanian GH, Bunney BJ (1973) Central dopaminergic neurons: neurophysiological identification and responses to drugs. In: Snyder SH, Usdin E (eds) Frontiers in catecholamine research. Pergamon Press, London, pp 643–648

    Google Scholar 

  • Albin GE, Young AB, Penney JP (1989) The functional anatomy of basal ganglia disorders. Trends Neurosci 12:366–375

    Article  CAS  PubMed  Google Scholar 

  • Alexander GE, Crutcher MD (1990) Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci 13:266–271

    Article  CAS  PubMed  Google Scholar 

  • Anderson JJ, Thomas NC, Engber TM (1992) Differential effect of subthalamic nucleus ablation on dopamine D1 and D2 agonist-induced rotation in 6-hydroxydopamine-lesioned rats. Brain Res 588:307–310

    Google Scholar 

  • Aziz TZ, Peggs D, Sambrook MA, Crossman AR (1991) Lesion of the subthalamic nucleus for the alleviation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the primate. Mov Disord 6:288–292

    CAS  PubMed  Google Scholar 

  • Bergman H, Wichmann T, Delong MR (1990) Reversal of experimental parkinsonism by lesions of the subthalamic nucleus. Science 249:1346–1348

    Google Scholar 

  • Boakes REJ, Bramwell GJ, Briggs I, Candy JM, Tampesta E (1974) Localization with pontamine sky blue of neurons in the brainstem responding to microiontophoresis applied compounds. Neuropharmacology 13:475–479

    Google Scholar 

  • Brotchie JM, Mitchell IJ, Sambrook MA, Crossman AR (1991) Alleviation of parkinsonism by antagonism of excitatory amino-acid transmission in the medial segment of the globus pallidus in rat and primate. Mov Disord 6:133–138

    Google Scholar 

  • Bunney BS, Chiodo LA, Grace A (1991) Midbrain dopamine system. Electrophysiological functioning: a review and new hypothesis. Synapse 9:79–94

    Google Scholar 

  • Carpenter MB, Whitter JR, Mettler FA (1950) Analysis of choreoid hyperkinesia in the rhesus monkey: surgical and pharmacological analysis of hyperkinesia resulting from lesions in the subthalamic nucleus of Luys. J Comp Neurol 92:293–332

    Google Scholar 

  • Canteras NS, Shammah-Lagnado SJ, Silva BA, Ricardo JA (1990) Afferent connections of the subthalamic nucleus: a combined retrograde and anterograde horseradish peroxydase study in the rat. Brain Res 513:43–59

    Google Scholar 

  • Carter DA, Fibiger HC (1978) The projections of the entopedoncular nucleus and globus pallidus in rat as demonstrated by autoradiography and horseradish peroxydase histochemistry. J Comp Neurol 177:113–124

    Google Scholar 

  • Cazalis M, Dayanithi G, Nordmann JJ (1985) The role of patterned burst and interburst interval on the excitation-coupling mechanism in the isolated rat neural lobe. J Physiol 369:45–60

    Google Scholar 

  • Chagnaud JL, Mons N, Tuffet S, Grandie-Vazeille X, Geffard M (1987) Monoclonal anti-bodies directed against glutaraldehyde-conjugated dopamine. J Neurochem 49:487–494

    Google Scholar 

  • Charlety PJ, Grenhoff J, Chergut K, DeLaChapelle B, Buda M, Svenson TH, Chouvet G (1991) Burst firing of mesencephalic dopamine neurons is inhibited by somatodentritic application of kynurenate. Acta Physiol Scand 142:105–112

    Google Scholar 

  • DeLong MR (1990) Primate model of movement disorders of basal ganglia origin. Trends Neurosci 13:281–285

    Article  CAS  PubMed  Google Scholar 

  • Deniau JM, Chevalier G (1985) Disinhibition as a basic process in the expression of striatal function. II. The striato-nigral influence on thalamocortical cells of the ventromedial thalamic nucleus. Brain Res 334:227–233

    Google Scholar 

  • DiChiara G, Morelli M (1984) Output pathways mediating basal ganglia function. In: McKenzie JS, Kemm RE, Wilcock LN (eds) The basal ganglia. Structure and function. Plenum Press, New York, pp 443–446

    Google Scholar 

  • DiChiara G, Morelli M, Porcedu ML, Gessa GL (1978) Evidence that nigral GABA mediates behavioural responses elicited by striatal receptors stimulation. Life Sci 23:2405–2052

    Google Scholar 

  • Féger J, Mouroux M, Benazzouz A, Boraud T, Gross C, Bevan M, Crossman (1994) The subthalamic nucleus: a more complex structure than expected. In: Percheron G, McKenzie JS, Féger J (eds) The basal ganglia. IV. New ideas and data on structure and function. Plenum Press, New York, pp 371–382

    Google Scholar 

  • Filion M, Tremblay L (1991) Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res 547:142–151

    Google Scholar 

  • Filion M, Tremblay L, Bedard P (1991) Effects of dopamine agonists on the spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism. Brain Res 547:152–161

    Article  CAS  PubMed  Google Scholar 

  • Fletcher GH, Starr MS (1987) Role of the substantia nigra in the expression of dopamine D1 receptor-mediated and D2 receptor-mediated behaviours. Neuroscience 23:1001–1010

    Google Scholar 

  • Gonon FG (1988) Non linear relatioship between impulse flow and dopamine release by rat midbrain dopaminergic neurons as studied by in vivo electrochemistry. Neuroscience 24:19–28

    Google Scholar 

  • Grace AA, Bunney BS (1984) The control of firing pattern in nigral dopamine neurons: bursting firing. J Neurosci 4:2866–2876

    Google Scholar 

  • Graham WC, Robertson RG, Sambrook MA, Crossman AR (1990) Injection of excitatory amino acid antagonists into the pallidal segment of the MPTP-treated primate reverses motor symptoms of parkinsonism. Life Sci 47:91–97

    Google Scholar 

  • Graybiel AM (1990) Neurotransmitters and neuromodulators in the basal ganglia. TINS 13:244–254

    Google Scholar 

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

    Google Scholar 

  • Hamada I, DeLong MR (1992a) Excitatory acid lesion of the primate subthalamic nucleus results in transient dyskinesias of the contralateral limbs. J Neurophysiol 68:1850–1858

    Google Scholar 

  • Hamada I, DeLong MR (1992b) Excitotoxic acid lesions of the primate subthalamic nucleus result in reduced pallidal neuronal activity during active holding. J Neurophysiol 68:1859–1866

    Google Scholar 

  • Hammond C, Féger I, Bioulac B, Souteyrand JP (1979) Experimental hemiballism in the monkey produced by unilateral kainic acid lesion in corpus Luysii. Brain Res 171:577–580

    Google Scholar 

  • Herrera-Marschitz M, Ungerstedt U (1984) Evidence that striatal efferents relate to different dopamine receptors. Brain Res 323:269–278

    Google Scholar 

  • Hollerman IR, Grace AA (1992) Subthalamic nucleus firing in the 6-OHDA treated rat: basal activity and responses to haloperidol. Brain Res 590:291–299

    Google Scholar 

  • Kitai ST, Kita H (1987) Anatomy and physiology of the subthalamic nucleus: a driving force of the basal ganglia. In: Carpenter MB, Jayaraman A (eds) The basal ganglia. II. Structure and function — current concepts. Plenum Press, New York, pp 357–373

    Google Scholar 

  • Klockgether T, Turski L (1990) NMDA antagonists potentiate antiparkinsonian actions of l-Dopa in monoamine-depleted rats. Ann Neurol 28:539–546

    Google Scholar 

  • McKenzie JS, Shafton AD, Stewart CA (1987) Motor responses to GABAergic interference in the rat ento-peduncular nucleus in relation to rotation behaviour. In: Carpenter MB, Jarayaman A (eds) The basal ganglia. II. Structure and function current concepts. Plenum Press, New York, pp 327–335

    Google Scholar 

  • Miller WC, Delong MR (1987) Altered tonic activity of neurons in the globus pallidus and subthalamic nucleus in the primate MPTP model of parkinsonism. In: Carpenter MB, Aghajanian A (eds) The basal ganglia. Plenum Press, New York, pp 415–427

    Google Scholar 

  • Morelli M, DiChiara G (1990) MK-801 potentiates dopaminergic D-1 but reduced D-2 responses in the 6-hydroxydopamine model of Parkinson disease. Eur J Pharmacol 182:611–612

    Google Scholar 

  • Murer MG, Pazo JH (1993) Circling behaviour induced by activation of GABAA receptors in the subthalamic nucleus. Neuroreport 4:1219–1922

    Google Scholar 

  • Nisenbaum ES, Stricker EM, Zigmond MJ, Berger TW (1986) Long term effect of dopamine-depleting brain lesions on spontaneous activity of type II striatal neurons: relation with behavioural recovery. Brain Res 398:221–230

    Google Scholar 

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

    Google Scholar 

  • Pan HS, Walters JR (1988) Unilateral lesion of the nigrostriatal pathway decrease the firing rate and alters the firing pattern of globus pallidus neurons in the rat. Synapse 2:650–656

    Google Scholar 

  • Parent A, Hazrati LN, Smith Y (1989) The subthalamic nucleus in primates. A neuroanatomical and immunohistochemical study. Curr Prob Neurol 9:29–35

    Google Scholar 

  • Paul ML, Graybel AM, David JC, Robertson HA (1992) D1-like and D2-like Dopamine receptors synergistically activate rotation and c-fos expression in the dopamine-depleted striatum in a rat model of parkinson disease. J Neurosci 12:3729–3742

    Google Scholar 

  • Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic, New York

    Google Scholar 

  • Pouchot C, Doudet D, Gross C, Bioulac B (1985) Activité des neurones de la pars réticulata de la substance noire après lésion du néostriatum ipsilatéral par l'acide kainique chez le rat. J Physiol 80:330–335

    Google Scholar 

  • Rinvik E, Otterson O (1993) Terminals of the subthalamonigral fibres are enriched with glutamate-like immunoreactivity: an electron microscopic, immunogold analysis in the cat. J Chem Neuroanat 6:19–30

    Google Scholar 

  • Robertson GS, Roberston HA (1986) Synergic effect of D1 and D2 dopamine agonists on turning behaviour in rats. Brain Res 384:387–390

    Google Scholar 

  • Robledo P, Féger J (1990) Excitatory influence of rat subthalamic nucleus to substantia nigra pars reticulata and the pallidal complex: electrophysiological data. Brain Res 518:47–54

    Google Scholar 

  • Robledo P, Féger J (1992) Acute monoaminergic depletion in the rat potentiates the excitatory effect of the subthalamic nucleus in the substantia nigra pars reticulata but not in the pallidal complexe. J Neural Transm Gen Sect 86:115–126

    Google Scholar 

  • Rouillard C, Bedard PJ (1987) Specific D1 and D2 dopamine agonists have synergic effects in the 6-hydroxydopamine circling model in the rat. Neuropharmacology 27:1257–1264

    Google Scholar 

  • Rouzaire-Dubois B, Scarnati E (1987) Pharmacological study of the cortical-induced excitation of subthalamic nucleus neurons in the rat: evidence for amino-acids as putative transmitters. Neuroscience 21:429–440

    Google Scholar 

  • Ryan LJ, Clark KB (1991) The role of the subthalamic nucleus in the response of globus pallidus neurons to stimulation of the prelimbic and agranular cortices in rats. Exp Brain Res 86:641–651

    Google Scholar 

  • Ryan LJ, Clark KB (1992) Alteration of neuronal responses in the subthalamic nucleus following globus pallidus and neostriatal lesions in rats. Brain Res Bull 29:319–327

    Google Scholar 

  • Ryan LJ, Sanders DJ, Clark KB (1992) Auto- and cross-correlation analysis of subthalamic nucleus neuronal activity in neostriatal-and globus pallidal-lesioned rats. Brain Res 583:253–261

    Google Scholar 

  • Ryan LJ, Sanders DJ (1993) Subthalamic nucleaus lesion regularizes firing pattern in globus pallidus and substantia nigra pars reticulata in rats. Brain Res 626:327–331

    Google Scholar 

  • Scheel Kruger J, Magelund G, Oliveras MC (1981) Role of GABA in the striatal output system: globus pallidus, nucleus entopedoncularis, substantia nigra and nucleus subthalamicus. In: Di-Chiara G., Gessa G (eds) GABA and the basal ganglia. Raven Press, New York, pp 165–186

    Google Scholar 

  • Smith IA, Grace AA (1992) Role of the subthalamic nucleus in the regulation of nigral dopamine neuron. Synapse 12:287–303

    CAS  PubMed  Google Scholar 

  • Smith Y, Parent A (1988) Neurons of the subthalamic nucleus in primates display glutamate but not GABA immunoreactivity. Brain Res 453:353–356

    Google Scholar 

  • Ungerstedt U (1971) Postsynaptic supersensitivity after 6-hydroxy-dopamine induced degeneration of the nigrostriatal dopamine system. Acta Physiol Scand Suppl 367:69–72

    CAS  PubMed  Google Scholar 

  • Van der Kooy D, Hattori T (1980) Single subthalamic nucleus neurons project to both the globus pallidus and substantia nigra in rat. Brain Res 192:751–768

    Google Scholar 

  • Waszczak BL, Lee EK, Tamminga CA, Walters JR (1984) Effect of dopamine system activation on substantia nigra pars reticulata output neurons: variable single unit responses in normals rats and inhibition in 6-hydroxydopamine-lesioned rats. J Neurosci 4:2369–2375

    Google Scholar 

  • Weick BG, Walters JR (1987a) Effects of D1 and D2 dopamine receptor stimulation on the activity of substantia nigra pars reticulata in 6-hydroxydopamine lesioned rats: D1/D2 coactivation induces potential responses. Brain Res 405:234–246

    Google Scholar 

  • Weick BG, Walters JR (1987b) D1 dopamine receptor stimulation potentiates neurophysiological effects of bromocriptine in rats with lesions of the nigro-striatal pathway. Neuropharmacology 26:641–644

    Google Scholar 

  • Weick BG, Engber TM, Susel Z, Chase TN, Walters JR (1990) Responses of substantia nigra pars reticulata neurons to GABA and SKF 38393 in 6-hydroxydopamine-lesioned rats are differentially affected by continuous and intermittent levodopa administration. Brain Res 523:16–22

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratoire de Neurophysiologie URA CNRS 1200, Université de Bordeaux II, 146 rue Léo Saignat, F-33076, Bordeaux, France

    P. Burbaud, C. Gross, A. Benazzouz & B. Bioulac

  2. Laboratoire d'Immunologie et Neuropathologie, Université de Bordeaux II, 146 rue Léo Saignat, F-33076, Bordeaux, France

    M. Coussemacq

Authors
  1. P. Burbaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Gross
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Benazzouz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Coussemacq
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. B. Bioulac
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Burbaud, P., Gross, C., Benazzouz, A. et al. Reduction of apomorphine-induced rotational behaviour by subthalamic lesion in 6-OHDA lesioned rats is associated with a normalization of firing rate and discharge pattern of pars reticulata neurons. Exp Brain Res 105, 48–58 (1995). https://doi.org/10.1007/BF00242181

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00242181

Key words

Search

Navigation