Dynamic-Clamp pp 217-235 | Cite as

Unraveling the Dynamics of Deep Cerebellar Nucleus Neurons with the Application of Artificial Conductances

Part of the Springer Series in Computational Neuroscience book series (NEUROSCI, volume 1)


In this chapter we demonstrate how dynamic clamping can be used to apply different types of conductances to neurons in the deep cerebellar nuclei (DCN) to explore how spiking in these neurons is controlled by the interaction of synaptic and intrinsic conductances. Besides the application of synaptic- and voltage-gated conductances, we introduce the modeling of an intracellular calcium pool in the real-time loop of the dynamic clamp in order to apply calcium-dependent conductances to DCN neurons in brain slices. Further, we report on our ongoing computer simulation studies, in which we compare the effects of focal somatic or distributed dendritic conductances on the spiking behavior of a full morphological DCN neuron model in order to better understand the limitations of dynamic clamping given by applying artificial conductances only at a single location.


Purkinje Cell Synaptic Input Spike Rate Climbing Fiber Deep Cerebellar Nucleus 



The work described in this chapter was not solely carried out by the authors. Volker Gauck obtained the dynamic-clamp recordings with inhibitory and NMDA conductances, Steven Feng programmed the HVA, Ca2+ pool, and sk conductance simulation into our LabVIEW dynamic clamp package and obtained the dynamic clamp data using these conductances. The work was supported by RO1 MH065634.


  1. Aizenman CD and Linden DJ (1999) Regulation of the rebound depolarization and spontaneous firing patterns of deep nuclear neurons in slices of rat cerebellum. J Neurophysiol 82:1697–1709.PubMedGoogle Scholar
  2. Alvina K and Khodakhah K (2008) Selective regulation of spontaneous activity of neurons of the deep cerebellar nuclei by N-type calcium channels in juvenile rats. J Physiol 27:27.Google Scholar
  3. Anchisi D, Scelfo B and Tempia F (2001) Postsynaptic currents in deep cerebellar nuclei. J Neurophysiol 85:323–331.PubMedGoogle Scholar
  4. Bernander O, Douglas RJ, Martin KAC et al (1991) Synaptic background activity influences spatiotemporal integration in single pyramidal cells. PNAS 88:11569–11573.PubMedCrossRefGoogle Scholar
  5. Bloedel JR (1992) Functional heterogeneity with structural homogeneity: How does the cerebellum operate? Behav Brain Sci 15:666–678.CrossRefGoogle Scholar
  6. De Schutter E and Bower JM (1994) An active membrane model of the cerebellar Purkinje cell I. Simulation of current clamp in slice. J Neurophysiol 71:375–400.PubMedGoogle Scholar
  7. Destexhe A, Rudolph M and Pare D (2003) The high-conductance state of neocortical neurons in vivo. Nat Rev Neurosci 4:739–751.PubMedCrossRefGoogle Scholar
  8. Feng S and Jaeger D (2008) The role of SK calcium-dependent potassium currents in regulating the activity of deep cerebellar nucleus neurons: A dynamic clamp study. Cerebellum 7:542–546.Google Scholar
  9. Fleidervish IA, Friedman A and Gutnick MJ (1996) Slow inactivation of Na+ current and slow cumulative spike adaptation in mouse and guinea-pig neocortical neurones in slices. J Physiol 493:83–97.PubMedGoogle Scholar
  10. Foehring RC (1996) Serotonin modulates N- and P-type calcium currents in neocortical pyramidal neurons via a membrane-delimited pathway. J Neurophysiol 75:648–659.PubMedGoogle Scholar
  11. Gauck V and Jaeger D (2000) The control of rate and timing of spikes in the deep cerebellar nuclei by inhibition. J Neurosci 20:3006–3016.PubMedGoogle Scholar
  12. Gauck V and Jaeger D (2003) The contribution of NMDA and AMPA conductances to the control of spiking in neurons of the deep cerebellar nuclei. J Neurosci 23:8109–8118.PubMedGoogle Scholar
  13. Holmes WR and Woody CD (1989) Effects of uniform and non-uniform synaptic ‘activation-distributions’ on the cable properties of modeled cortical pyramidal neurons. Brain Res 505:12–22.PubMedCrossRefGoogle Scholar
  14. Jaeger D (2003) No parallel fiber volleys in the cerebellar cortex: evidence from cross-correlation analysis between Purkinje cells in a computer model and in recordings from anesthetized rats. J Comput Neurosci 14:311–327.PubMedCrossRefGoogle Scholar
  15. Jaeger D and Bower JM (1999) Synaptic control of spiking in cerebellar Purkinje cells: Dynamic current clamp based on model conductances. J Neurosci 19:6090–6101.PubMedGoogle Scholar
  16. Jaeger D, DeSchutter E and Bower JM (1997) The role of synaptic and voltage-gated currents in the control of Purkinje cell spiking: A modeling study. J Neurosci 17:91–106.PubMedGoogle Scholar
  17. LeDoux MS, Hurst DC and Lorden JF (1998) Single-unit activity of cerebellar nuclear cells in the awake genetically dystonic rat. Neuroscience 86:533–545.PubMedCrossRefGoogle Scholar
  18. Lisberger SG and Fuchs AF (1978) Role of primate flocculus during rapid behavioral modification of vestiubloocular reflex. I. Purkinje cell activity during visually guided horizontal smooth-pursuit eye movements and passive head rotation. J Neurophysiol 41:733–763.PubMedGoogle Scholar
  19. Llinás R and Sugimori M (1980) Electrophysiological properties of in vitro Purkinje cell somata in mammalian cerebellar slices. J Physiol 305:171–195.PubMedGoogle Scholar
  20. Napper RMA and Harvey RJ (1988) Number of parallel fiber synapses on an individual Purkinje cell in the cerebellum of the rat. J Comp Neurol 274:168–177.PubMedCrossRefGoogle Scholar
  21. Palkovits M, Mezey E, Hamori J et al (1977) Quantitative histological analysis of the cerebellar nuclei in the cat. I. Numerical data on cells and synapses. Exp Brain Res 28:189–209.PubMedCrossRefGoogle Scholar
  22. Pineda JC, Waters RS and Foehring RC (1998) Specificity in the interaction of HVA Ca2+ channel types with Ca2+-dependent AHPs and firing behavior in neocortical pyramidal neurons. J Neurophysiol 79:2522–2534.PubMedGoogle Scholar
  23. Raman IM, Gustafson AE and Padgett D (2000) Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. J Neurosci 20:9004–9016.PubMedGoogle Scholar
  24. Robinson HP and Kawai N (1993) Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons. J Neurosci Meth 49:157–165.CrossRefGoogle Scholar
  25. Rowland NC and Jaeger D (2005) Coding of tactile response properties in the rat deep cerebellar nuclei. J Neurophysiol 94:1236–1251.PubMedCrossRefGoogle Scholar
  26. Rudolph M, Pelletier JG, Pare D et al (2005) Characterization of synaptic conductances and integrative properties during electrically induced EEG-activated states in neocortical neurons in vivo. J Neurophysiol 94:2805–2821.PubMedCrossRefGoogle Scholar
  27. Sharp AA, O’Neil MB, Abbott LF et al (1993) Dynamic clamp: computer-generated conductances in real neurons. J Neurophysiol 69:992–995.PubMedGoogle Scholar
  28. Steuber V, Mittmann W, Hoebeek FE et al (2007) Cerebellar LTD and pattern recognition by Purkinje cells. Neuron 54:121–136.PubMedCrossRefGoogle Scholar
  29. Stratton SE, Lorden JF, Mays LE et al (1988) Spontaneous and harmaline-stimulated Purkinje cell activity in rats with a genetic movement disorder. J Neurosci 8:3327–3336.PubMedGoogle Scholar
  30. Suter KJ and Jaeger D (2004) Reliable control of spike rate and spike timing by rapid input transients in cerebellar stellate cells. Neuroscience 124:305–317.PubMedCrossRefGoogle Scholar
  31. Telgkamp P and Raman IM (2002) Depression of inhibitory synaptic transmission between Purkinje cells and neurons of the cerebellar nuclei. J Neurosci 22:8447–8457.PubMedGoogle Scholar
  32. Thach WT (1968) Discharge of purkinje and cerebellar nuclear neurons during rapidly alternating arm movements in the monkey. J Neurophysiol 31:785–797.PubMedGoogle Scholar
  33. Welsh JP and Llinas R (1997) Some organizing principles for the control of movement based on olivocerebellar physiology. Prog Brain Res 114:449–461.PubMedCrossRefGoogle Scholar
  34. Womack MD and Khodakhah K (2004) Dendritic control of spontaneous bursting in cerebellar Purkinje cells. J Neurosci 24:3511–3521.PubMedCrossRefGoogle Scholar
  35. Xia XM, Fakler B, Rivard A et al (1998) Mechanism of calcium gating in small-conductance calcium-activated potassium channels. Nature 395:503–507.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of BiologyEmory UniversityAtlantaUSA

Personalised recommendations