Journal of Computational Neuroscience

, Volume 20, Issue 3, pp 299–320 | Cite as

A computational model of how an interaction between the thalamocortical and thalamic reticular neurons transforms the low-frequency oscillations of the globus pallidus

  • Arash Hadipour-NiktarashEmail author


In Parkinson’s disease, neurons of the internal segment of the globus pallidus (GPi) display the low-frequency tremor-related oscillations. These oscillatory activities are transmitted to the thalamic relay nuclei. Computer models of the interacting thalamocortical (TC) and thalamic reticular (RE) neurons were used to explore how the TC-RE network processes the low-frequency oscillations of the GPi neurons. The simulation results show that, by an interaction between the TC and RE neurons, the TC-RE network transforms a low-frequency oscillatory activity of the GPi neurons to a higher frequency of oscillatory activity of the TC neurons (the superharmonic frequency transformation). In addition to the interaction between the TC and RE neurons, the low-threshold calcium current in the RE and TC neurons and the hyperpolarization-activated cation current (I h) in the TC neurons have significant roles in the superharmonic frequency transformation property of the TC-RE network. The external globus pallidus (GPe) oscillatory activity, which is directly transmitted to the RE nucleus also displays a significant modulatory effect on the superharmonic frequency transformation property of the TC-RE network.


Thalamus Basal ganglia Globus pallidus Oscillations Computational models Frequency transformation Parkinson’s disease 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Asanuma C (1994) GABAergic and pallidal terminals in the thalamic reticular nucleus of squirrel monkeys. Exp. Brain Res. 101: 439–451.CrossRefPubMedGoogle Scholar
  2. Bal T, McCormick DA (1996) What stops synchronized thalamocortical oscillations? Neuron 17: 297–308.CrossRefPubMedGoogle Scholar
  3. Bar-Gad I, Bergman H (2001) Stepping out of the box: Information processing in the neural networks of the basal ganglia. Curr. Opin. Neurobiol. 11: 689–695.CrossRefPubMedGoogle Scholar
  4. Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ (1998) Cellular and network models for intrathalamic augmenting responses during 10-Hz stimulation. J. Neurophysiol. 79: 2730–2748.PubMedGoogle Scholar
  5. Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ (1999) Self-sustained rhythmic activity in the thalamic reticular nucleus mediated by depolarizing GABA(A) receptor potentials. Nature Neurosci. 2: 168–174.CrossRefPubMedGoogle Scholar
  6. Bergman H, Wichmann T, Karmon B, Delong MR (1994) The primate subthalamic nucleous: II. Neuronal activity in the MPTP model of parkinsonism. J. Neurophysiol. 72: 507–520.PubMedGoogle Scholar
  7. Bergman H, Deuschl G (2002) Pathophysiology of parkinson’s disease: from clinical neurology to basic neuroscience and back. Mov. Disord. 17: S28–S40.CrossRefPubMedGoogle Scholar
  8. Beurrier C, Congar P, Bioulac B, Hammond C (1999) Subthalamic nucleus neurons switch from single-spike activity to burst-firing mode. J. Neurosci. 19: 599–609.PubMedGoogle Scholar
  9. Carr J (2002) Tremor in Parkinson’s disease. Parkinsonism and related disorders 8: 223–234.CrossRefPubMedGoogle Scholar
  10. Chesselet MF, Delfs JM (1996) Basal ganglia and movement disorders: An update. 19: 417–422.Google Scholar
  11. Cox CL, Sherman SM (1999) Glutamate inhibits thalamic reticular neurons. J. Neurosci. 19: 6694–6699.PubMedGoogle Scholar
  12. Destexhe A, Babloyantz A, Sejnowski TJ (1993a) Ionic mechanisms for intrinsic slow oscillations in thalamic relay neurons. Biophys J. 65: 1538–52.PubMedCrossRefGoogle Scholar
  13. Destexhe A, McCormick DA, Sejnowski TJ (1993b) A model for 8–10 Hz spindling in interconnected thalamic relay and reticularis neurons. Biophys. J. 65: 2474–2478.Google Scholar
  14. Destexhe A, Contreras D, Sejnowski TJ, Steriade M (1994a) A model of spindle rhythmicity in the isolated thalamic reticular nucleus. J. Neurophysiol. 72: 803–818.PubMedGoogle Scholar
  15. Destexhe A, Mainen ZF, Sejnowski TJ (1994b) Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism. J. Comput. Neurosci. 1: 195–230.CrossRefPubMedGoogle Scholar
  16. Destexhe A, Bal T, McCormick DA, Sejnowski TJ (1996a) Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices. J. Neurophysiol. 76: 2049–2070.PubMedGoogle Scholar
  17. Destexhe A, Contreras D, Steriade M, Sejnowski TJ, Huguenard JR (1996b) In vivo, in vitro, and computational analysis of dendritic calcium currents in thalamic reticular neurons J. Neurosci. 16: 169–185.PubMedGoogle Scholar
  18. Destexhe A, Contreras D, Steriade M (1998) Mechanisms underlying the synchronizing action of corticothalamic feedback through inhibition of thalamic relay cells. J. Neurophysiol. 79: 999–1016.Google Scholar
  19. Destexhe A, Sejnowski TJ (2002) The initiation of bursts in thalamic neurons and the cortical control of thalamic sensitivity. Phil. Trans. R. Soc. Lond. 357: 1649–1657.Google Scholar
  20. Destexhe A, Sejnowski TJ (2003) Interactions between membrane conductances underlying thalamocortical slow-wave oscillations. Physiol. Rev. 83: 1401–1453.PubMedGoogle Scholar
  21. Deuschl G, Bain P, Brin M (1998) Consensus statement of the movement disorder society on tremor. Ad Hoc Scientific Committee. Mov. Disord. 13(suppl. 3): 2–23.Google Scholar
  22. Deuschl G, Raethjen J, Baron R, Lindemann M, Wilms H, Krack P (2000) The pathophysiology of parkinsonian tremor: A review. J. Neurol. 247: v/33–v/48.CrossRefGoogle Scholar
  23. Elble RJ (1996) Central mechanisms of tremor. J. Clin. Neurophysiol. 13: 133–144.CrossRefPubMedGoogle Scholar
  24. Elble RJ (1997) The pathophysiology of tremor. In RL Watts, WC Koller, eds., Movement Disorders, McGraw Hill, New York, p. 405.Google Scholar
  25. Gandia JA, De Las Heras S, Garcia M, Gimenez-Amaya JM (1993) Afferent projections to the reticular thalamic nucleus from the globus pallidus and the substantia nigra in the rat. Brain Res. Bull. 32: 351–358.CrossRefPubMedGoogle Scholar
  26. Guehl D, Pessiglione M, Francois C, Yelnik J, Hirsch EC, Feger J, Tremblay L (2003) Tremor-related activity of neurons in the ‘motor’ thalamus: Changes in firing rate and pattern in the MPTP vervet model of parkinsonism. Eur. J. Neurosci. 17: 2388–2400.CrossRefPubMedGoogle Scholar
  27. Guillery RW, Harting JK (2003) Structure and connections of the thalamic reticular nucleus: Advancing views over half a century. J. Comp. Neurol. 463: 360–371.CrossRefPubMedGoogle Scholar
  28. Hadipour Niktarash A (2003) Transmission of the subthalamic nucleus oscillatory activity to the cortex: A computational approach. J. Comput. Neurosci. 15: 223–232.CrossRefPubMedGoogle Scholar
  29. Hadipour Niktarash A, Shahidi GA (2004) effects of the activity of the internal globus pallidus-pedunculopontine loop on the transmission of the subthalamic nucleus-external globus pallidus-pacemaker oscillatory activities to the cortex. J. Comput. Neurosci. 16: 113–127.CrossRefPubMedGoogle Scholar
  30. Hazrati LN, Parent A (1991) Projection from the external pallidum to the reticular thalamic nucleus in the squirrel monkey. Brain Res. 550: 142–146.CrossRefPubMedGoogle Scholar
  31. Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J. Physiol. (Lond) 117: 500–544.Google Scholar
  32. Huguenard JR, Coulter DA, McCormick DA (1991) A fast transient potassium current in thalamic relay neurons: Kinetics of activation and inactivation. J. Neurophysiol. 66: 1305–1315.Google Scholar
  33. Huguenard JR, McCormick DA (1992) Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons. J. Neurophysiol. 68: 1373–1383.PubMedGoogle Scholar
  34. Huguenard JR, Prince DA (1992) A novel T-type current underlies prolonged Ca2+ dependent burst firing in GABAergic neurons of rat thalamic reticular nucleus. J. Neurosci. 12: 3804–3817.PubMedGoogle Scholar
  35. Hurtado JM, Gray CM, Tamas LB, Sigvardt KA (1999) Dynamics of tremor-related oscillations in the human globus pallidus: A single case study. Proc. Natl. Acad. Sci. USA 96: 1674–1679.Google Scholar
  36. Hutchison WD, Lozano AM, Tasker PR, Lang AE, Dostrovsky JO (1997) Identification and characterization of neurons with tremor-frequency activity in human globus pallidus. Exp. Brain Res. 113: 557–563.CrossRefPubMedGoogle Scholar
  37. Ilinsky IA, Yi H, Kultas-Ilinsky (1997) Mode of termination of pallidal afferents to the thalamus: A light and electron microscopic study with anterograde tracers and immunocytochemistry in Macaca mulatta. J. Comp. Neurol. 386: 601–612.CrossRefPubMedGoogle Scholar
  38. Kaneoke Y, Vitek JL (1995) The motor thalamus in the parkinsonian primate: Enhanced burst and oscillatory activities. Soc. Neurosci. Abstr. 21: 1428.Google Scholar
  39. Laitinen LV, Bergenheim AT, Hariz MI (1992) Ventroposterolateral pallidotomy can abolish all parkinsonian symptoms. Stereotact. Funct. Neurosurg. 58: 14–21.Google Scholar
  40. Lamarre, Y., Central mechanisms of experimental tremor and their clinical relevance. In LJ Findley, R Capildeo, eds., Handbook of Tremor Disorders, Vol. 1, Marcel Dekker, New York, 1995, p. 103.Google Scholar
  41. Le Masson G, Le Masson S, Debay D, Bal T (2002) Feedback inhibition controls spike transfer in hybrid thalamic circuits. Nature 417: 854–858.CrossRefPubMedGoogle Scholar
  42. Lemstra AW, Metman LV, Lee JI, Dougherty PM, Lenz FA (1999) Tremor-frequency (3–6 Hz) activity in the sensorimotor arm representation of the internal segment of the globus pallidus in patients with Parkinson’s disease. Neurosci. Lett. 267: 129–132.CrossRefPubMedGoogle Scholar
  43. Lenz FA, Tasker RR, Kwan HC, Schnider S, Kwong R, Murayama Y, Dostrovsky JO, Murphy JT (1988) Single unit analysis of the human ventral thalamic nuclear group: Correlation of thalamic tremor cells with the 3–6 Hz component of parkinsonian tremor. J Neurosci. 8: 754–764.PubMedGoogle Scholar
  44. Lenz FA, Kwan HC, Martin RL, Tasker RR, Dostrovsky JO, Lenz YE (1994) Single unit analysis of the human ventral thalamic nuclear group. Tremor-related activity in functionally identified cells. Brain 117: 531–543.PubMedGoogle Scholar
  45. Levy R, Hutchison WD, Lozano AM, Dostrovsky JO (2002) Synchronized neuronal discharge in the basal ganglia of Parkinsonian patients is limited to oscillatory activity. J Neurosci. 22: 2855–2861.PubMedGoogle Scholar
  46. Liu XB, Jones EG (1999) Predominance of corticothalamic synaptic inputs to thalamic reticular nucleus neurons in the rat. J. Comp. Neurol. 414: 67–79.CrossRefPubMedGoogle Scholar
  47. Lüthi A, McCormick DA (1998) H-current: Properties of a neuronal and network pacemaker. Neuron 21: 9–12.CrossRefPubMedGoogle Scholar
  48. Lytton WW, Destexhe A, Sejnowski TJ (1996) Control of slow oscillations in the thalamocortical neuron: A computer model. Neuroscience 70: 673–684.CrossRefPubMedGoogle Scholar
  49. McCormick DA, Pape HC (1990) Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurons. J. Physiol. (Lond.) 431: 291–318.Google Scholar
  50. McCormick DA, Huguenard JR (1992) A model of electrophysiological properties of thalamocortical relay neurons. J. Neurophysiol. 68: 1384–1400.PubMedGoogle Scholar
  51. McCormick DA, Bal T (1997) Sleep and arousal: Thalamocortical mechanisms. Annu. Rev. Neurosci. 20: 185–215.CrossRefPubMedGoogle Scholar
  52. Magnin M, Morel A, Jeanmonod D (2000) Single-unit analysis of the pallidum, thalamus and subthalamic nucleus in parkinsonian patients. Neuroscience 96: 549–564.CrossRefPubMedGoogle Scholar
  53. Nambu A, Llinãs R (1994) Electrophysiology of globus pallidus neurons in vitro. J Neurophysiol 72: 1127–1139.PubMedGoogle Scholar
  54. Ni Z, Bouali-Benazzouz R, Gao D, Benabid AL, Benazzouz A (2000) Changes in the firing pattern of globus pallidus neurons after the degeneration of nigrostriatal pathway are mediated by the subthalamic nucleus in the rat. Eur. J. Neurosci. 12: 4338–4344.CrossRefPubMedGoogle Scholar
  55. Nini A, Fiengold A, Slovin H, Bergman H (1995) Neurons in the globus pallidus do not show correlated activity in the normal monkey but phase-locked oscillations appear in the MPTP model of parkinsonism. J. Neurophysiol. 74: 1800–1805.PubMedGoogle Scholar
  56. Ohye C, Saito U, Fukamachi A, Narabayashi H (1974) An analysis of the spontaneous rhythmic and non-rhythmic burst discharges in the human thalamus. J. Neurol. Sci. 22: 245–259.CrossRefPubMedGoogle Scholar
  57. Pare D, Curro Dossi R, Steriade M (1990) Neuronal basis of the parkinsonian resting tremor: A hypothesis and its implications for treatment.. Neuroscience 35: 217–226.Google Scholar
  58. Parent A, Hazrati LN (1995) Functional anatomy of the basal ganglia. Part I: The cortico-basal ganglia-thalamo-cortical loop. Brain Res. Rev. 20: 91–127.CrossRefPubMedGoogle Scholar
  59. Paulson HL, Stern MB (1997) Clinical manifestation s of Parkinson’s disease. In RL. Watts, WC Koller, eds., Movement Disorders. Vol. 1, McGraw Hill, New York, p. 183.Google Scholar
  60. Pinault D (2004) The thalamic reticular nucleus: Structure, function and concept. Brain Res. Rev. 46: 1–31.CrossRefPubMedGoogle Scholar
  61. Plenz D, Kitai ST (1999) A basal ganglia pacemaker formed by the subthalamic nucleus and external globus pallidus. Nature 400: 677–682.CrossRefPubMedGoogle Scholar
  62. Raz A, Vaadia E, Bergman H (2000) Firing patterns and correlations of spontaneous 0discharge of pallidal neurons in the normal and the tremulous 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine Vervet model of parkinsonism. J. Neurosci. 20: 8559–8571.PubMedGoogle Scholar
  63. Rodriguez MC, Guridi OJ, Alvarez L, Mewes K, Macias R, Vitek J, DeLong MR, Obeso JA (1998) The subthalamic nucleus and tremor in parkinson’s disease. Mov. Disord. 13: 111–118.PubMedCrossRefGoogle Scholar
  64. Sanchez-Vives MV, McCormick DA (1997) Functional properties of prigeniculate inhibition of dorsal lateral geniculate nucleus thalamocortical neurons in vitro. J. Neurosci. 17: 8880–8893.PubMedGoogle Scholar
  65. Sanchez-Vives MV, Bal T, McCormick DA (1997) Inhibitory interactions between prigeniculate GABAergic neurons. J. Neurosci. 17: 8894–8908.PubMedGoogle Scholar
  66. Sherman SM, Guillery RW (2001) Exploring the Thalamus. Academic Press, San Diego, pp. 144–167.Google Scholar
  67. Soltesz I, Lightowler S, Leresche N, Jassik-Gerschenfeld D, Pollard CE, Crunelli V (1991) Two inward currents and the transformation of low frequency oscillations of rat and cat thalamocortical cells. J. Physiol. 441: 175–197.PubMedGoogle Scholar
  68. Steriade M, McCormick DA, Sejnowski TJ (1993) Thalamocortical oscillations in the sleeping and aroused brain. Science 262: 679–685.PubMedGoogle Scholar
  69. Terman D, Rubin JE, Yew AC, Wilson CJ (2002) Activity patterns in a model for the subthalamopallidal network of the basal ganglia. J. Neurosci. 22: 2963–2976.PubMedGoogle Scholar
  70. Toth T, Crunelli V. (1992) Computer simulations of the pacemaker oscillations of thalamocortical cells. Neuroreport 3: 65–68.PubMedCrossRefGoogle Scholar
  71. Traub RD, Miles R (1991) Neural networks of hippocampus: Cambridge University Press, Cambridge.Google Scholar
  72. Ulrich D, Huguenard JR (1997) Nucleus-specific chloride homeostasis in rat thalamus. J. Neurosci. 17: 2348–2354.PubMedGoogle Scholar
  73. Ulrich D, Huguenard JR (1996) γ-Aminobutyric acid type B receptor-dependent burst –firing in thalamic neurons: A dynamic clamp study. Proc. Natl. Acad. Sci. USA 93: 13245–13249.Google Scholar
  74. Vitek JL, Hashimoto T, Peoples J, DeLong MR, Bakay RA (2004) Acute stimulation in the external segment of the globus pallidus improves parkinsonian motor signs. Mov. Disord. 19: 907–915.CrossRefPubMedGoogle Scholar
  75. Volkmann J, Sturm V, Weiss P, Kappler J, Voges J, Koulousakis A, Lehrke R, Hefter H, Freund HJ (1998) Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson’s disease. Ann. Neurol. 44: 953–961.Google Scholar
  76. von Krosigk M, Bal T, McCormick DA (1993) Cellular mechanisms of a synchronized oscillation in the thalamus. Science 261: 361–364.PubMedGoogle Scholar
  77. Wang XJ, Golomb D, Rinzel J (1995) Emergent spindle oscillations and intermittent burst firing in a thalamic model: Specific neuronal mechanisms. Proc. Natl. Acad. Sci. USA 92: 5577–5581.Google Scholar
  78. Wichmann T, DeLong MR (2003) Pathophysiology of Parkinson’s disease: The MPTP primate model of the human disorder. Ann. N.Y. Acad. Sci. 991: 199–213.PubMedCrossRefGoogle Scholar
  79. Yamamoto T, Hassler R, Huber C, Wagner A, Sasaki K (1983) Electrophysiologic studies on the pallido- and cerebellothalamic projections in squirrel monkeys (Saimiri sciureus). Exp. Brain Res. 51: 77–87.PubMedGoogle Scholar
  80. Yamamoto T, Noda T, Miyata M, Nishimura Y (1984) Electrophysiological and morphological studies on thalamic neurons receiving entopedunculo- and cerebello-thalamic projections in the cat. Brain Res. 301: 231–242.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  1. 1.Department of Biomedical Engineering, Laboratory for Computational Motor ControlJohns Hopkins School of MedicineBaltimoreUSA
  2. 2.Institute for Studies in Theoretical Physics and Mathematics (IPM)School of Cognitive SciencesTehranIran

Personalised recommendations