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Cognitive Neurodynamics

, Volume 6, Issue 4, pp 333–341 | Cite as

Modeling effect of GABAergic current in a basal ganglia computational model

  • Felix NjapEmail author
  • Jens Christian Claussen
  • Andreas Moser
  • Ulrich G. Hofmann
Research Article

Abstract

Electrical high frequency stimulation (HFS) of deep brain regions is a method shown to be clinically effective in different types of movement and neurological disorders. In order to shed light on its mode of action a computational model of the basal ganglia network coupled the HFS as injection current into the cells of the subthalamic nucleus (STN). Its overall increased activity rendered a faithful transmission of sensorimotor input through thalamo-cortical relay cells possible. Our contribution uses this model by Rubin and Terman (J Comput Neurosci, 16, 211–223, 2004) as a starting point and integrates recent findings on the importance of the extracellular concentrations of the inhibiting neurotransmitter GABA. We are able to show in this computational study that besides electrical stimulation a high concentration of GABA and its resulting conductivity in STN cells is able to re-establish faithful thalamocortical relaying, which otherwise broke down in the simulated parkinsonian state.

Keywords

Computational model Synaptic conductances γ-Aminobutyric acid Deep brain stimulation Parkinsonian condition 

Notes

Acknowledgments

This work was supported by the “Graduate School for Computing in Medicine and Life Sciences” funded by Germany‘s Excellence Initiative [DFGGSC235/1].

References

  1. Alejandro P (2006) Working with a computational model for high frequency stimulation. Rapport de recherche. http://hal.inria.fr/inria-00071378/en/
  2. Baker PM, Pennefather PS, Oser BA, Skinner FS (2002) Disruption of coherent oscillations in inhibitory networks with anesthetics: role of GABAA receptor desensitization. J Neurophysiol 88:2821–2833PubMedCrossRefGoogle Scholar
  3. Benabid A (2007) What the future holds for deep brain stimulation. Expert Rev Med Devices 4:895–903PubMedCrossRefGoogle Scholar
  4. Benabid A, Benazzouz A, Pollak P (2002) Mechanisms of deep brain stimulation. Mov. Disorders 17:73–74CrossRefGoogle Scholar
  5. Boyes J, Bolam JP (2007) Localization of GABA receptors in the basal ganglia. Prog Brain Res 160:229–243PubMedCrossRefGoogle Scholar
  6. Braun HA, Huber MT, Anthes N, Voigt K, Neiman A, Pei X, Moss F (2000) Interactions between slow and fast conductances in the Huber/Braun model of cold-receptor discharges. Neurocomputing 32–33:51–59CrossRefGoogle Scholar
  7. Chakravarthy VS, Denny J, Bapi RS (2010) What do the basal ganglia do? A modeling perspective. Biol Cybern 103:237–253PubMedCrossRefGoogle Scholar
  8. Deep-Brain Stimulation for Parkinson’s Disease Study Group (2001) Deep-brain stimulation of the subthalamic nucleus or the pars interna of the globus pallidus in parkinson’s disease. New Eng J Med 345:956–963CrossRefGoogle Scholar
  9. Dostrovsky JO, Levy R, Wu JP, Hutchison WD, Tasker RR, Lozano AM (2000) Microstimulation-induced inhibition of neuronal firing in human globus pallidus. J Neurophysiol 84:570–574PubMedGoogle Scholar
  10. Ermentrout B (2002) Simulating, analyzing, and animating dynamical systems: a guide to XPPAUT for researchers and student. SIAM Press, PhiladelphiaCrossRefGoogle Scholar
  11. Feuerstein TJ, Kammerer M, Lücking CH, Moser A (2011) Selective GABA release as a mechanistic basic of high-frequency stimulation used for the treatment of neuropsychiatric diseases. Naunyn-Schmiedberg’s Arch Pharmacol. 384(1):1–20CrossRefGoogle Scholar
  12. Foster BL, Bojak I, Liley DTJ (2008) Population based models of cortical drug response: insights from anaesthesia. Cogn Neurodyn 2:283–296PubMedCrossRefGoogle Scholar
  13. Fox RF (1997) Stochastic versions of the Hodgkin-Huxley equations Biophys. J. 72(5):2068–2074Google Scholar
  14. Garcia L, D’Allexandro G, Bioulac B, Hammond C (2005) High frequency stimulation in parkinson’s disease: more or less? Trends Neurosci 28(4):209–216PubMedCrossRefGoogle Scholar
  15. Gerstner W, Kistler W (2002) Spiking neuron models. Single neurons, populations, plasticity. Cambridge University Press, CambridgeCrossRefGoogle Scholar
  16. Gong HY, Zhang YY, Liang PJ, Zhang PM (2010) Neural coding properties based on spike toming and pattern correlation of retinal ganglia cells. Cogn Neurodyn 4:337–346PubMedCrossRefGoogle Scholar
  17. Guo Y, Rubin JE, McIntyre CC, Vitek JJ, Terman D (2008) Thalamocortical relay fidelity varies across subthalamic nucleus deep brain stimulation protocols in a data driven computational model. J Neurophysiol 99:1477–1492PubMedCrossRefGoogle Scholar
  18. Higham DJ (2001) An algorithmic introduction to numerical simulation of stochastic differential equations. SIAM Rev 43:525–546CrossRefGoogle Scholar
  19. Hiller A, Loeffler S, Haupt C, Litza M, Hofmann UG, Moser A (2007) Electrical high frequency stimulation of the caudate nucleus induces local GABA outflow in freely moving rats. J. Neurosci Meth 159:286–290CrossRefGoogle Scholar
  20. Hutt A, Longtin A (2010) Effects of the anesthetic agent propofol on neural populations. Cogn Neurodyn 4:37–59PubMedCrossRefGoogle Scholar
  21. Liu Y, Wang R, Zhang Z, Jiao X (2010) Analysis of stability of neural network with inhibitory neurons. Cogn Neurodyn 4(1):61–68PubMedCrossRefGoogle Scholar
  22. Magarinos-Ascone C, Pazo JH, Macadar O, Buno W (2002) High-frequency stimulation of the subthalamic nucleus silences subthalamic nucleus: a possible cellular mechanism in parkinson’s disease. Neuroscience 115:1109–1117PubMedCrossRefGoogle Scholar
  23. Mantovani M, Van Velthoven V, Fuellgraf H, Feuerstein TJ, Moser A (2006) Neuronal electrical high frequency stimulation enhances GABA outflow from human neocortical slices. Neurochem Int 49:347–350PubMedCrossRefGoogle Scholar
  24. Mantovani M, Moser A, Haas AC, Zentner J, Feuerstein TJ (2009) GABAA autoreceptors enhance GABA release from human neocortex: towards a mechanism for high-frequency stimulation (HFS) in Brain? Naunyn-Schmiedberg’s Arch Pharmacol 380:45–58CrossRefGoogle Scholar
  25. Mayer J, Schuster HG, Claussen JC (2006) The role of inhibitory feedback for information processing in thalamocortical circuits. Phys Rev E 73:031908CrossRefGoogle Scholar
  26. McIntyre CC, Savasta M, Walter LB, Vitek JL (2004) How does deep brain stimulation work? Present understanding and future questions. J Clin Neurophys 21:40–50CrossRefGoogle Scholar
  27. Moran A, Stein E, Tischler H, Bar-Gad I (2012) Decoupling neuronal oscillations during subthalamic nucleus stimulation in the parkinsonian primate. Neurobiol Disease 45:583–590CrossRefGoogle Scholar
  28. Njap F, Claussen JC, Moser A, Hofmann UG (2011) Comparing realistic subthalamic nucleus neuron models. AIP Conf Proc 1371:102–109CrossRefGoogle Scholar
  29. Olanow W, Brin M, Obeso J (2000) The role of deep brain stimulation as a surgical treatment for parkinson’s disease. Neurology 55(6):S60–S66PubMedGoogle Scholar
  30. Park C, Worth RM, Rubchinsky LL (2011) Neural dynamics in parkinson brain: the boundary between synchronized and nonsynchronized dynamics. Phys Rev E 83:042901CrossRefGoogle Scholar
  31. Pirini M, Rocchini L, Sensi M, Chiari L (2009) A computational modeling approach to investigate different targets in deep brain stimulation for parkinson’s disease. J Comput Neurosci 26:91–107PubMedCrossRefGoogle Scholar
  32. Qu J, Wang R, Du Y, Cao J (2011) Synchronization study in ring-like and grid-like neuronal networks. Cogn Neurodyn. doi: 10.1007/s11571-011-9174-9 Google Scholar
  33. Rubin JE, Terman D (2004) High frequency stimulation of the subthalamic nucleus eliminates pathological thalamic rhythmicity in a computational model. J Comput Neurosci 16:211–223PubMedCrossRefGoogle Scholar
  34. Skinner F, Kopell N, Mardr E (1994) Mechanisms for oscillations and frequency control in network of mutually inhibitory relaxation oscillators. J Comp Neurosci 1:69–87CrossRefGoogle Scholar
  35. Wang X-J, Rinzel J (1992) Alternating and synchronous rythms in reciprocally inhibitory model neurons. Neural Comp 4:84–97CrossRefGoogle Scholar
  36. White J, Chow C, Ritt J, Soto-Trevino C, Kopell N (1998) Synchronization and oscillatory dynamics in heterogeneous, mutually inhibited neurons. J Comput Neurosci 5:5–16PubMedCrossRefGoogle Scholar
  37. Wilson CJ, Beverlin B II, Netoff T (2011) Chaotic desynchronization as the therapeutic mechanism of deep brain stimulation. Front Syst Neurosci 5:50. doi: 10.3389/fnsys.2011.00050 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Felix Njap
    • 1
    • 2
    Email author
  • Jens Christian Claussen
    • 2
    • 4
  • Andreas Moser
    • 3
  • Ulrich G. Hofmann
    • 1
  1. 1.Institute for Signal ProcessingUniversity of LübeckLübeckGermany
  2. 2.Graduate School for Computing Medicine and Life SciencesUniversity of LübeckLübeckGermany
  3. 3.Department of NeurologyUniversity of LübeckLübeckGermany
  4. 4.Institute for Neuro-and BioinformaticsUniversity of LübeckLübeckGermany

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