Summary
1. Individual neurons were recorded extracellularly in the precentral forelimb area of two monkeys trained to perform rapid, large amplitude flexion and extension movements of the contralateral forearm in response to auditory signals. Electromyographic (EMG) activity in the biceps/triceps muscles was recorded separately under the same conditions. The dopaminergic (DA) neurons of the substantia nigra (SN) were destroyed selectively by repeated series of intravenous injections of MPTP. The lesion was verified on serial slices using both tyrosine hydroxylase immunocytochemistry and classical staining methods. 2. In normal monkeys, the frequency of firing of precentral neurons shows rapid changes shortly before the onset of displacement. In our sample (n= 102), most of the neurons (49%) tested during movement in both directions (flexion, extension) showed a reciprocal pattern of activity for the two directions of movement, a small percentage (19%) exhibited a change for only one direction (unidirectional neurons), and the remaining 32% displayed a similar change for both directions of movement (bidirectional neurons). 3. In MPTP-treated monkeys, movement-related modification of neuronal activity was more gradual, beginning earlier and lasting longer relative to the onset of movement. The cellular reaction time (the time between the auditory cue and a significant change in neuronal activity) was not significantly altered. Spontaneous firing of precentral neurons (n = 124) did not increase significantly, and the dynamic discharge rate was unchanged after the nigral lesion. However, only 18% of cortical neurons still presented a reciprocal pattern of discharge for the two directions of movement, while the percentage of unidirectional neurons increased (50%), and the percentage of bidirectional neurons remained the same (32%). 4. After MPTP treatment, alterations in movement parameters and EMG activity were observed. Mean reaction time and movement duration increased by 20–25% and 25–30% respectively. The movements were slower and were associated with a generalised depression in the shape and the amplitude of EMG activity in the agonist muscle. 5. The neuronal basis for the observed central and peripheral disturbance in the MPTP-treated monkeys is discussed. We conclude that SN lesion leads to two main disturbances of cortical activity: i) the loss of the reciprocal pattern of response of movement-related cortical cells, and ii) an inability of the motor cortex to modify its activity in response to peripheral input.
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References
Adams R, Van Bogaert L, Van Der Eecken H (1961) Dégénérescences nigro-striées et cérébello-nigro-striées. Psychiat Neurol (Basel) 142:219–259
Asanuma H (1981) The pyramidal tract. In: Geiger SR (ed) Handbook of physiology, Vol II. The nervous system. Am Physiol Soc, Bethesda, pp 703–733
Asanuma H, Arissian K (1984) Experiments on functional role of peripheral input to motor cortex during voluntary movements in the monkey. J Neurophysiol 52:212–227
Asanuma H, Rosen I (1972) Topographical organization of cortical efferent zones projecting to distal forelimb muscles in the monkey. Exp Brain Res 14:243–256
Bathien N (1978) Réflexes médullaires chez l'homme et leur contrôle supra-segmentaire. In: Hecaen H, Jeannerod H (eds) Du contrôle moteur à l'organisation du geste. Masson, Paris, pp 52–72
Berger B, Trottier S, Gaspar P, Verney C, Alvarez C (1986) Major dopamine innervation of the cortical motor areas in the cynomolgus monkey: a radioautographic study with comparative assessment of serotonergic afferents. Neurosci Lett 72:121–127
Besson JM, Cheramy A, Feltz P, Glowinski J (1971) Dopamine spontaneous and drug-induced release from the caudate nucleus in the cat. Brain Res 32:407–437
Brons JF, Woody CD (1980) Long term changes in excitability of cortical neurons after Pavlovian conditioning and extinction. J Neurophysiol 44:605–615
Burns RS, Chiueh CC, Markey SP, Ebert MH, Jacobowitz DM, Kopin IJ (1983) A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Proc Natl Acad Sci USA 80:4546–4550
Carpenter MB (1981) Anatomy of the corpus striatum and brain stem integrating systems. In: Geiger SR (ed) Handbook of physiology, Vol II. The nervous system. Am Physiol Soc, Bethesda, pp 947–995
Cheney PD, Fetz EE (1980) Functional classes of primate cortico-motoneuronal cells and their relation to active force. J Neurophysiol 44:773–791
Davis GC, Williams AC, Markey SP, Ebert MH, Caine ED, Reichert CM, Kopin IJ (1979) Chronic parkinsonism secondary to intravenous injection of meperidine analogues, Psychiat Res 1:249–254
Degryse AD, Colpaert FC (1986) Symptoms and behavioral features induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in an old Java monkey (Macaca cynomolgus fascicularis (Raffles)). J Brain Res Bull 16:561–571
Delong MD, Crutche RM, Georgopoulos AP (1983) Relations between movement and single cell discharge in the substantia nigra of the behaving monkey. J Neurosci 3:1599–1606
Delong MR, Georgopoulos AP (1981) Motor functions of the basal ganglia. In: Geiger SR (ed) Handbook of physiology, Vol II. The nervous system. Am Physiol Soc, Bethesda, pp 1017–1061
Deutch AY, Elsworth JD, Goldstein M, Fuxe K, Redmond DE, Sladek JR, Roth RH (1986) Preferential vulnerability of A8 dopamine neurons in the primate to the neurotoxin 1-methyl-4phenyl-1,2,3,6-tetrahydro-pyridine. Neurosci Lett 68:51–56
Doudet D, Gross Ch, Lebrun-Grandié Ph, Bioulac B (1985) MPTP primate model of Parkinson's disease: a mechanographic and electromyographic study. Brain Res 335:194–199
Evarts EV (1974) Precentral and postcentral cortical activity in association with visually triggered movement. J Neurophysiol 37:373–381
Evarts EV (1981) Role of motor cortex in voluntary movements in primate. In: Geiger SR (ed) Handbook of physiology, Vol II. The nervous system. Am Physiol Soc, Bethesda, pp 1083–1120
Evarts EV, Teravainen NH, Calne DB (1981) Reaction time in Parkinson's disease. Brain 104:167–186
Féger J (1981) Les ganglions de la base: aspects anatomiques et électrophysiologiques. J Physiol (Paris) 77:7–44
Fetz EE, Finocchio DV, Baker MA, Soso MJ (1980) Sensory motor responses of precentral cortex cells during comparable passive and active joint movements. J Neurophysiol 43:451–498
Flowers K (1978) Some frequency response characteristics of parkinsonism on pursuit tracking. Brain 101:19–34
Filion M (1979) Effects of interruption of the nigrostriatal pathway and of dopaminergic agents on the spontaneous activity of globus pallidus neurons in the awake monkey. Brain Res 178:425–441
Filion M, Boucher R, Bedard P (1985) Globus pallidus unit activity in the monkey during the induction of parkinsonism by 1-methyl-4-phenyl-1,2,3,6-tetra-hydro-pyridine (MPTP). Soc Neurosci Abstr 340
François C, Percheron G, Yelnik J, Heyner S (1985) A histological atlas of the macaque (Macaca mul'atta) substantia nigra in ventricular coordinates. Brain Res Bull 14:349–367
Gross Ch, Féger J, Seal J, Haramburu P, Bioulac B (1983) Neuronal activity in area 4 and movement parameters recorded in trained monkeys after unilateral lesion of the substantia nigra. Exp Brain Res Suppl 7:181–193
Gupta M, Gupta BK, Thomas R, Bruemmer V, Sladek JR Jr, Felten DL (1986) Aged mice are more sensitive to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treatment than young adults. Neurosci Lett 70:326–331
Hallet M, Khosbin S (1980) A physiological mechanism of bradykinesia. Brain 103:301–314
Hikosaka O, Wurtz RH (1983) Visual and oculomotor functions of monkey substantia nigra pars reticulata. IV. Relation of substantia nigra to superior colliculus. J Neurophysiol 49:1285–1301
Horak FB, Anderson ME (1984a) Influence of globus pallidus on arm movement in monkeys. I. Effects of kainic acid-induced lesions. J Neurophysiol 52:290–304
Horak FB, Anderson ME (1984b) Influence of globus pallidus on arm movement in monkeys. II. Effects of stimulation. J Neurophysiol 52:305–322
Hornykiewicz O (1982) Brain neurotransmitters changes in Parkinson's disease. In: Marsden CD, Fahn S (eds) Movement disorder, II. Butterworth Scientific, London, pp 41–58
Jacobowitz DM, Burns RS, Chiueh CC, Kopin IJ (1984) N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes destruction of the nigrostriatal but not the mesolimbic dopamine system in the monkey. Psychopharmacol Bull 20:416–422
Kluver H, Barrera E (1953) A method for the combined staining of cells and fibers in the nervous system. J Neuropath Exp Neurol 12:400–403
Kopin IJ, Markey SP (1988) MPTP activity: implications for research in Parkinson's disease. Ann Rev Neurosci 11:81–96
Lamarre Y (1975) Tremorgenic mechanisms in primate. In: Meldrum BS, Marsden CD (eds) Primate models of neurological disorders. Raven Press, New York (Adv Neurol 10:23–34)
Lamarre Y, Joffroy A, Fillion M, Bouchoux R (1978) A stereotaxic method for repeated sessions of central unit recording in the paralyzed or moving animal. Rev Canad Biol 29:371–376
Lamarre Y, Spidalieri G, Lund JP (1981) Patterns of muscular and motor cortical activity during a simple arm movement in the monkey. Can J Physiol Pharmacol 59:748–756
Langston JW, Ballard PA (1984) Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): implication for treatment and the pathogenesis of Parkinson's disease. Can J Neurol Sci 11:160–165
Langston JW, Forno LS, Rebert CS, Irwin I (1984) Selective nigral toxicity after systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the squirrel monkey. Brain Res 292:390–394
Langsten JW, Irwin I (1986) MPTP-current concepts and controversies. Clin Neuropharmacol 9:485–507
Lindvall O, Bjorklund A (1979) Dopaminergic innervation of the globus pallidus by collaterals from the nigrostriatal pathway. Brain Res 172:169–173
Marsden CD (1982) The mysterious motor function of the basal ganglia: the Robert Wartenberg lecture. Neurology 32:514–539
Miller WC, Mitchell SJ, Baker FH, Delong MR (1986) Neuronal activity in primate globus pallidus following MPTP treatment. In: Neural control of limb movement. Abstract Satellite symposium of XXX international meeting of the IUPS. A-40
Mitchell IJ, Cross AJ, Sambrook MA, Crossman AR (1985) Sites of the neurotoxic action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in the macaque monkey include the ventral tegmental area and the locus coeruleus. Neurosci Lett 61:195–200
Narabayashi H (1987) Similarity and dissimilarity of MPTP models to Parkinson's disease: importance of juvenile parkinsonism. Eur Neurol 26:24–29
Ohye C (1981) Neural mechanism of tremor. Adv Neurol Sci 25:106–117
Ruffieux A, Schultz W (1980) Dopaminergic activation of reticulata neurons in the substantia nigra. Nature 285:240–241
Schell GR, Strick PL (1984) The origin of thalamic inputs to the arcuate premotor and supplementary motor areas. J Neurosci 4:539–560
Schieber MH, Thach T Jr (1985) Trained slow tracking. I. Muscular production of wrist movement. J Neurophysiol 54:1213–1227
Schneider JS, Markham CH (1986) Neurotoxic effects of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the cat:tyrosine hydroxylase immunohistochemistry. Brain Res 373:258–267
Schultz W (1988) MPTP-induced parkinsonisms in monkeys: mechanism of action, selectively and pathophysiology. Gen Pharmacol 19:153–161
Schultz W, Aebischer R, Ruffieux A (1983) The encoding of motor acts by the substantia nigra. Exp Brain Res Suppl 7:171–180
Selby C (1975) Parkinson's disease. In: Vinken PJ, Bruyn GW (eds) Handbook for clinical neurology, Vol 6. North Holland Pub Comp., Amsterdam, pp 173–211
Tanji J, Evarts EV (1976) Anticipatory activity of motor cortex neurons in relation to an intended movement. J Neurophysiol 39:1062–1068
Viallet F, Trouche E, Beaubaton D, Nieoullon A, Legallet E (1983) Motor impairment after electrolytic lesions of the substantia nigra in baboons: behavioral data with quantitative and kinematic analysis of a pointing movement. Brain Res 279:193–206
Weinrich M, Wise SP (1982) The premotor codes of the monkey. J Neurosci 2:1329–1345
York DH (1978) Alterations in spinal monosynaptic reflex produced by stimulations of the substantia nigra. In: Yahr MD (ed) Corticothalamic projections and sensory motor activities. Raven Press, New York, pp 445–447
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Doudet, D.J., Gross, C., Arluison, M. et al. Modifications of precentral cortex discharge and EMG activity in monkeys with MPTP-induced lesions of DA nigral neurons. Exp Brain Res 80, 177–188 (1990). https://doi.org/10.1007/BF00228859
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DOI: https://doi.org/10.1007/BF00228859