This study summarizes results from studies of behavior and visuomotor functions in monkeys (rhesus macaques) during development of parkinsonism-like syndrome induced by chronic administration of small doses of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). An operant conditioned reflex method was used to study the amplitude-time parameters of visually evoked saccades. Development of MPTP-induced syndrome was associated with increases in the latent periods of saccades, decreases in their peak velocities, and degradation of their accuracy. These oculomotor effects were apparent at the presymptomatic stage of MPTP syndrome, such that they can be regarded as early markers of parkinsonism-like syndrome in monkeys. The development of MPTP syndrome produced cognitive and motor deficits on execution of a spatially hindered operant task consisting of a food-procuring manipulation in peripersonal space.
Similar content being viewed by others
References
Armstrong, R. A., “Parkinson’s disease and the eye,” Ophthal. Physiol. Opt., 17, Suppl. 2, S9–S16 (1997).
Armstrong, R. A., “Visual symptoms in Parkinson’s disease,” Parkinsons Dis., 2011, Art. ID 908306 (2011), doi: 10.4061/2011/908306.
Baziyan, B. Kh., Chigaleichik, L. A., and Dmitriev, I. E., “Possible mechanisms of impairment of saccadic eye movements in patients with Parkinson’s disease,” Byul. Eksperim. Biol, 125, No. 3, 254–259 (1998).
Benazzouz, A., Gross, C., Dupont, J., and Bioulac, B., “MPTP induced hemiparkinsonism in monkeys: behavioral, mechanographic, electromyographic and immunohistochemical studies,” Exp. Brain Res., 90, No. 1, 116–120 (1992).
Bezard, E., Dovero, S., Prunier, C., et al., “Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine-lesioned macaque model of Parkinson’s disease,” J. Neurosci., 21, No. 17, 6853–6861 (2001).
Blekher, T., Weaver, M., Rupp, J., et al., “Multiple step pattern as a biomarker in Parkinson disease,” Parkinsonism Relat. Disord., 15, No. 7, 506–510 (2009).
Boulet, S., Mounayar, S., Poupard, A., et al., “Behavioral recovery in MPTP-treated monkeys: neurochemical mechanisms studied by intrastriatal microdialysis,” J. Neurosci., 28, No. 38, 9575–9584 (2008).
Briand, K. A., Hening, W., Poizner, H., and Sereno, A. B., “Automatic orienting of visuospatial attention in Parkinson’s disease,” Neuropsychologia, 39, No. 11, 1240–1249 (2001).
Brooks, B. A., Fuchs, A. F., and Finocchio, D., “Saccadic eye movement deficits in the MPTP monkey model of Parkinson’s disease,” Brain Res., 383, No. 1–2, 402–407 (1986).
Chambers, J. M. and Prescott, T. J., “Response times for visually guided saccades in persons with Parkinson’s disease: a meta-analytic review,” Neuropsychologia, 48, No. 4, 887–899 (2010).
Chan, F., Armstrong, I. T., Pari, G., et al., “Deficits in saccadic eye-movement control in Parkinson’s disease,” Neuropsychologia, 43, No. 5, 784–796 (2005).
Jones, G. M. and DeJong, J. D., “Dynamic characteristics of saccadic eye movements in Parkinson’s disease,” Exp. Neurol., 31, No. 1, 17–31 (1971).
Kimmig, H., Haußmann, K., Mergner, T., and Lücking, C. H., “What is pathological with gaze shift fragmentation in Parkinson’s disease?” J. Neurology, 249, No. 6, 683–692 (2002).
Kingstone, A., Klein, R., Morein-Zamir, S., et al., “Orienting attention in aging and Parkinson’s disease: Distinguishing modes of control,” J. Clin. Exp. Neuropsychol., 24, No. 7, 951–967 (2002).
Kori, A., Miyashita, N., Kato, M., et al., “Eye movements in monkeys with local dopamine depletion in the caudate nucleus. II. Deficits in voluntarysaccades,” J. Neurosci., 15, No. 1, 928–941 (1995).
Latanov, A. V., Tereshchenko, L. V., Yudin, A. G., and Shul’govskii, V. V., “Residual impairments to operant behavior in moneys after curing of MPTP-induced parkinsonism-like syndrome,” Ross. Fiziol. Zh., 83, No. 1–2, 155–158 (1997).
MacAskill, M. R., Graham, C. F., Pitcher, T. L., et al., “The influence of motor and cognitive impairment upon visually-guided saccades in Parkinson’s disease,” Neuropsychologia, 50, No. 14, 3338–3347 (2012).
Mosimann, U. P., Müri, R. M., Burn, D. J., et al., “Saccadic eye movement changes in Parkinson’s disease dementia and dementia with Lewy bodies,” Brain, 128, No. 6, 1267–1276 (2005).
Mounayar, S., Boulet, S., Tandé, D., et al., “A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery,” Brain, 130, No. 11, 2898–2914 (2007).
Nakamura, T., Kanayama, R., Sano, R., et al., “Quantitative analysis of ocular movements in Parkinson’s disease,” Acta Otolaryngol., Supplement, 481, 559–562 (1991).
Pessiglione, M., Guehl, D., Agid, Y., et al., “Impairment of context-adapted movement selection in a primate model of presymptomatic Parkinson’s disease,” Brain, 126, No. 6, 1392–408 (2003).
Porras, G., Li, Q., and Bezard, E., “Modeling Parkinson’s disease in primates: The MPTP model,” Cold Spring Harb. Perspect. Med., 2, No. 3, a009308 (2012).
Ratmanova, P. O., Napalkov, D. A., Bogdanov, R. R., et al., “Effects of dopamine deficiency of the process of preparation of visually evoked saccadic eye movements,” Zh. Vyssh. Nerv. Deyat., 56, No. 5, 590–596 (2006).
Robinson, D. A., “A method of measuring eye movement using a scleral search coil in a magnetic field,” IEEE Trans. Biomed. Eng., 10, No. 4, 137–145 (1963).
Rottach, K. G., Riley, D. E., DiScenna, A. O., et al., “Dynamic properties of horizontal and vertical eye movements in parkinsonian syndromes,” Ann. Neurol., 39, No. 3, 368–377 (1996).
Schneider, J. S. and Kovelowski, C. J., “Chronic exposure to low doses of MPTP. I. Cognitive deficits in motor asymptomatic monkeys,” Brain Res., 519, No. 1, 122–128 (1990).
Schneider, J. S. and Pope-Coleman, A., “Cognitive deficits precede motor deficits in a slowly progressing model of parkinsonism in the monkey,” Neurodegeneration, 4, No. 3, 245–255 (1995).
Schultz, W., Romo, R., Scarnati, E., et al., “Saccadic reaction times, eye–arm coordination and spontaneous eye movements in normal and MPTPtreated monkeys,” Exp. Brain Res., 78, No. 2, 253–267 (1989a).
Schultz, W., Studer, A., Romo, R., et al., “Deficits in reaction times and movement times as correlates of hypokinesia in monkeys with MPTP-induced striatal dopamine depletion,” J. Neurophysiol., 6, No. 1, 65l–668 (1989b).
Shul’govskii, V. V., Latanov, A. V., and Petrov, G. V., “Dopaminergic mechanisms of oculomotor behavior in primates,” Vestn. Ross. Akad. Med. Nauk, 1, No. 1, 49–52 (1994).
Silva, M. F., Faria, P., Regateiro, F. S., et al., “Independent patterns of damage within magno-, parvo-and koniocellular pathways in Parkinson’s disease,” Brain, 128, No. 10, 2260–2271 (2005), DOI: 10. 1093/brain/awh581.
Slovin, H., Abeles, M., Vaadia, E., et al., “Frontal cognitive impairments and saccadic deficits in low-dose MPTP-treated monkeys,” J. Neurophysiol., 81, No. 2, 858–874 (1999).
Tereshchenko, L. V., Anisimov, V. T., Shul’govsky, V. V., and Latanov, A. V., “Early changes of saccade parameters in monkeys at the developments of MPTP-induced hemiparkinsonism,” Perception, 44, No. 8–9, 1054–1063 (2015).
Tereshchenko, L. V., Kuznetsov, Yu. B., Latanov, A. V., and Shul’govskii, V. V., “A method for chronic electromagnetic recording of eye and head movements in monkeys,” Zh. Vyssh. Nerv. Deyat., 50, No. 5, 889–894 (2000).
Tereshchenko, L. V., Molchanov, S. A., Kolesnikova, O. V., et al., “Asymmetry of the amplitude-time properties of targeted saccades in monkeys depending on the complexity of the spatial visual stimulation scheme,” Zh. Vyssh. Nerv. Deyat., 55, No. 5, 639–646 (2005).
Tereshchenko, L. V., Yudin, A. G., Kuznetsov, Yu. B., et al., “Impairments to saccadic eye movements on development of MPTP-induced syndrome in monkeys,” Byul. Eksperim. Biol, 133, No. 2, 215–218 (2002).
Ungerleider, L. G. and Mishkin, M., “Two cortical visual systems,” in: Analysis of Visual Behavior, Ingle, D. J. et al., MIT Press, Cambridge, MA (1982), pp. 549–586.
Weil, R. S., Schrag, A. E., Warren, J. D., et al., “Visual dysfunction in Parkinson’s disease,” Brain, 139, No. 11, 2827–2843 (2016), doi: https://doi.org/10.1093/brain/aww175.
White, O. B., Saint-Cyr, J. A., Tomlinson, R. D., and Sharpe, J. A., “Ocular motor deficits in Parkinson’s disease. II. Control of the saccadic and smooth pursuit systems,” Brain, 106, No. 3, 571–587 (1983).
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 68, No. 4, pp. 496–513, July–August, 2018.
Rights and permissions
About this article
Cite this article
Tereshchenko, L.V., Latanov, A.V. Impairments to Visuomotor Functions on Development of MPTP-Induced Parkinsonism-Like Syndrome in Monkeys. Neurosci Behav Physi 49, 1106–1117 (2019). https://doi.org/10.1007/s11055-019-00847-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11055-019-00847-4