The Cerebellum

, Volume 16, Issue 2, pp 293–305 | Cite as

Long Pauses in Cerebellar Interneurons in Anesthetized Animals

  • Ronit Givon-Mayo
  • Shlomi Haar
  • Yoav Aminov
  • Esther Simons
  • Opher DonchinEmail author
Original Paper


Are long pauses in the firing of cerebellar interneurons (CINs) related to Purkinje cell (PC) pauses? If PC pauses affect the larger network, then we should find a close relationship between CIN pauses and those in PCs. We recorded activity of 241 cerebellar cortical neurons (206 CINs and 35 PCs) in three anesthetized cats. One fifth of the CINs and more than half of the PCs were identified as pausing. Pauses in CINs and PCs showed some differences: CIN mean pause length was shorter, and, after pauses, only CINs had sustained reduction in their firing rate (FR). Almost all pausing CINs fell into same cluster when we used different methods of clustering CINs by their spontaneous activity. The mean spontaneous firing rate of that cluster was approximately 53 Hz. We also examined cross-correlations in simultaneously recorded neurons. Of 39 cell pairs examined, 14 (35 %) had cross-correlations significantly different from those expected by chance. Almost half of the pairs with two CINs showed statistically significant negative correlations. In contrast, PC/CIN pairs did not often show significant effects in the cross-correlation (12/15 pairs). However, for both CIN/CIN and PC/CIN pairs, pauses in one unit tended to correspond to a reduction in the firing rate of the adjacent unit. In our view, our results support the possibility that previously reported PC bistability is part of a larger network response and not merely a biophysical property of PCs. Any functional role for PC bistability should probably be sought in the context of the broader network.


Cerebellar interneurons Molecular layer interneuron Cerebellum Pauses Bistability 



We would like to thank the staff of the Soroka MRI facility—particularly Assaf Kreh and Dr. Ilan Shelef—who were tirelessly helpful in imaging and image processing. Dr. Shira Ovadia provided veterinary oversight and helpful scientific and technical suggestions. We would like to thank Prof. Eilon Vaadia and Prof. Hagai Bergman for helping us in the first but critical steps of this research.

This research was supported by the Israeli Science Foundation (ISF) grant number 624/06 and the Lower Saxony/Israel Foundation.

Compliance with Ethical Standards

Conflict of Interest

No conflict of interest

Supplementary material

12311_2016_792_MOESM1_ESM.pdf (251 kb)
ESM 1 (PDF 250 kb)
12311_2016_792_MOESM2_ESM.pdf (322 kb)
ESM 2 (PDF 321 kb)
12311_2016_792_MOESM3_ESM.pdf (857 kb)
ESM 3 (PDF 857 kb)
12311_2016_792_MOESM4_ESM.pdf (228 kb)
ESM 4 (PDF 228 kb)
12311_2016_792_MOESM5_ESM.pdf (246 kb)
ESM 5 (PDF 245 kb)
12311_2016_792_MOESM6_ESM.pdf (1.4 mb)
ESM 6 (PDF 1475 kb)


  1. 1.
    Rokni D, Tal Z, Byk H, Yarom Y. Regularity, variability and bi-stability in the activity of cerebellar purkinje cells. Front. Cell. Neurosci. [Internet]. 2009 [cited 2015 Jan 6];3:12. Available from:
  2. 2.
    Oldfield CS, Marty A, Stell BM. Interneurons of the cerebellar cortex toggle Purkinje cells between up and down states. Proc. Natl. Acad. Sci. U. S. A. [Internet]. 2010 [cited 2015 Jan 6];107:13153–8. Available from:
  3. 3.
    Cooke SF, Attwell PJE, Yeo CH. Temporal properties of cerebellar-dependent memory consolidation. J. Neurosci. [Internet]. 2004 [cited 2015 Jan 6];24:2934–41. Available from: Scholar
  4. 4.
    Wulff P, Goetz T, Leppä E, Linden A-M, Renzi M, Swinny JD, et al. From synapse to behavior: rapid modulation of defined neuronal types with engineered GABAA receptors. Nat. Neurosci. [Internet]. 2007 [cited 2015 Jan 6];10:923–9. Available from:
  5. 5.
    Wulff P, Schonewille M, Renzi M, Viltono L, Sassoè-Pognetto M, Badura A, et al. Synaptic inhibition of Purkinje cells mediates consolidation of vestibulo-cerebellar motor learning. Nat. Neurosci. [Internet]. 2009 [cited 2014 Nov 29];12:1042–9. Available from:
  6. 6.
    Häusser M, Clark BA. Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron [Internet]. 1997 [cited 2015 Jan 6];19:665–78. Available from: Scholar
  7. 7.
    Raman IM, Bean BP. Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons. J. Neurosci. [Internet]. 1997 [cited 2015 Jan 6];17:4517–26. Available from: Scholar
  8. 8.
    Raman IM, Bean BP. Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. J. Neurosci. [Internet]. 1999 [cited 2015 Jan 6];19:1663–74. Available from: Scholar
  9. 9.
    Eccles JC, Llinás R, Sasaki K. The excitatory synaptic action of climbing fibres on the Purkinje cells of the cerebellum. J. Physiol. [Internet]. 1966 [cited 2015 Jan 6];182:268–96. Available from:
  10. 10.
    Brunel N, Hakim V, Isope P, Nadal J-P, Barbour B. Optimal information storage and the distribution of synaptic weights: perceptron versus Purkinje cell. Neuron [Internet]. 2004 [cited 2014 Dec 17];43:745–57. Available from: Scholar
  11. 11.
    Mittmann W, Koch U, Häusser M. Feed-forward inhibition shapes the spike output of cerebellar Purkinje cells. J. Physiol. [Internet]. 2005 [cited 2014 Nov 29];563:369–78. Available from:
  12. 12.
    Mittmann W, Häusser M. Linking synaptic plasticity and spike output at excitatory and inhibitory synapses onto cerebellar Purkinje cells. J. Neurosci. [Internet]. 2007 [cited 2015 Jan 6];27:5559–70. Available from: Scholar
  13. 13.
    Wise AK, Cerminara NL, Marple-Horvat DE, Apps R. Mechanisms of synchronous activity in cerebellar Purkinje cells. J Physiol. 2010;588:2373–90.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Shin S-L, De Schutter E. Dynamic synchronization of Purkinje cell simple spikes. J. Neurophysiol. [Internet]. 2006 [cited 2016 May 3];96:3485–91. Available from:
  15. 15.
    De Schutter E, Steuber V. Patterns and pauses in Purkinje cell simple spike trains: experiments, modeling and theory. Neuroscience. 2009. p. 816–26.Google Scholar
  16. 16.
    Person AL, Raman IM. Synchrony and neural coding in cerebellar circuits. Front. Neural Circuits [Internet]. 2012;6:97. Available from: 10.3389/fncir.2012.00097/abstract
  17. 17.
    Bengtsson F, Geborek P, Jörntell H. Cross-correlations between pairs of neurons in cerebellar cortex in vivo. Neural Netw. [Internet]. 2013 [cited 2014 Dec 17];47:88–94. Available from:
  18. 18.
    Mann-Metzer P, Yarom Y. Electrotonic coupling interacts with intrinsic properties to generate synchronized activity in cerebellar networks of inhibitory interneurons. J. Neurosci. [Internet]. 1999 [cited 2015 Jan 6];19:3298–306. Available from: Scholar
  19. 19.
    Dugué GP, Brunel N, Hakim V, Schwartz E, Chat M, Lévesque M, et al. Electrical coupling mediates tunable low-frequency oscillations and resonance in the cerebellar Golgi cell network. Neuron [Internet]. 2009 [cited 2014 Dec 6];61:126–39. Available from: Scholar
  20. 20.
    Williams SR, Christensen SR, Stuart GJ, Häusser M. Membrane potential bistability is controlled by the hyperpolarization-activated current I(H) in rat cerebellar Purkinje neurons in vitro. J. Physiol. [Internet]. 2002 [cited 2015 Jan 6];539:469–83. Available from:
  21. 21.
    Loewenstein Y, Mahon S, Chadderton P, Kitamura K, Sompolinsky H, Yarom Y, et al. Bistability of cerebellar Purkinje cells modulated by sensory stimulation. Nat. Neurosci. [Internet]. 2005 [cited 2014 Dec 24];8:202–11. Available from: Scholar
  22. 22.
    Schonewille M, Khosrovani S, Winkelman BHJ, Hoebeek FE, De Jeu MTG, Larsen IM, et al. Purkinje cells in awake behaving animals operate at the upstate membrane potential. Nat. Neurosci. [Internet]. 2006 [cited 2015 Jan 6];9:459–61; author reply 461. Available from: Scholar
  23. 23.
    Shin S-L, Hoebeek FE, Schonewille M, De Zeeuw CI, Aertsen A, De Schutter E. Regular patterns in cerebellar Purkinje cell simple spike trains. PLoS One [Internet]. 2007 [cited 2015 Jan 6];2:e485. Available from:
  24. 24.
    Steuber V, Mittmann W, Hoebeek FE, Silver RA, De Zeeuw CI, Häusser M, et al. Cerebellar LTD and pattern recognition by Purkinje cells. Neuron [Internet]. 2007 [cited 2014 Dec 15];54:121–36. Available from:
  25. 25.
    Tal Z, Chorev E, Yarom Y. State-dependent modification of complex spike waveforms in the cerebellar cortex. Cerebellum [Internet]. 2008 [cited 2015 Jan 6];7:577–82. Available from: Scholar
  26. 26.
    Cheron G, Prigogine C, Cheron J, Márquez-Ruiz J, Traub RD, Dan B. Emergence of a 600-Hz buzz UP state Purkinje cell firing in alert mice. Neuroscience [Internet]. 2014 [cited 2015 May 27];263:15–26. Available from:
  27. 27.
    Servais L, Bearzatto B, Hourez R, Dan B, Schiffmann SN, Cheron G. Effect of simple spike firing mode on complex spike firing rate and waveform in cerebellar Purkinje cells in non-anesthetized mice. Neurosci. Lett. [Internet]. 2004 [cited 2015 May 27];367:171–6. Available from:
  28. 28.
    Fernandez FR, Engbers JDT, Turner RW. Firing dynamics of cerebellar purkinje cells. J. Neurophysiol. [Internet]. 2007 [cited 2015 Jan 6];98:278–94. Available from: Scholar
  29. 29.
    Jacobson GA, Rokni D, Yarom Y. A model of the olivo-cerebellar system as a temporal pattern generator. Trends Neurosci. [Internet]. 2008 [cited 2014 Dec 8];31:617–25. Available from: Scholar
  30. 30.
    Engbers JDT, Fernandez FR, Turner RW. Bistability in Purkinje neurons: ups and downs in cerebellar research. Neural Netw. [Internet]. 2013 [cited 2015 May 13];47:18–31. Available from:
  31. 31.
    Clopath C, Nadal J-P, Brunel N. Storage of correlated patterns in standard and bistable Purkinje cell models. PLoS Comput. Biol. [Internet]. 2012 [cited 2015 Apr 12];8:e1002448. Available from:
  32. 32.
    Maex R, Steuber V. An integrator circuit in cerebellar cortex. Eur. J. Neurosci. [Internet]. 2013 [cited 2015 May 27];38:2917–32. Available from: Scholar
  33. 33.
    Yartsev MM, Givon-Mayo R, Maller M, Donchin O. Pausing purkinje cells in the cerebellum of the awake cat. Front. Syst. Neurosci. [Internet]. 2009 [cited 2014 Dec 28];3:2. Available from:
  34. 34.
    Trapani G, Altomare C, Liso G, Sanna E, Biggio G. Propofol in anesthesia. Mechanism of action, structure-activity relationships, and drug delivery. Curr Med Chem. 2000;7:249–71.CrossRefPubMedGoogle Scholar
  35. 35.
    Lahti AC, Weiler MA, Michaelidis T, Parwani A, Tamminga CA. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology. 2001;25:455–67.CrossRefPubMedGoogle Scholar
  36. 36.
    Haar S, Givon-Mayo R, Barmack NH, Yakhnitsa V, Donchin O. Spontaneous activity does not predict morphological type in cerebellar interneurons. J. Neurosci. [Internet]. 2015 [cited 2015 Jan 29];35:1432–42. Available from:
  37. 37.
    Ruigrok TJH, Hensbroek RA, Simpson JI. Spontaneous activity signatures of morphologically identified interneurons in the vestibulocerebellum. J. Neurosci. [Internet]. 2011 [cited 2015 Jan 6];31:712–24. Available from:
  38. 38.
    Kita H, Kita T. Role of striatum in the pause and burst generation in the globus pallidus of 6-OHDA-treated rats. Front. Syst. Neurosci. [Internet]. 2011 [cited 2015 Jan 6];5:42. Available from:
  39. 39.
    Legéndy CR, Salcman M. Bursts and recurrences of bursts in the spike trains of spontaneously active striate cortex neurons. J. Neurophysiol. [Internet]. 1985 [cited 2015 Jan 6];53:926–39. Available from: Scholar
  40. 40.
    Hensbroek RA, Ruigrok TJH, van Beugen BJ, Maruta J, Simpson JI. Visuo-vestibular information processing by unipolar brush cells in the rabbit flocculus. Cerebellum [Internet]. 2015 [cited 2015 Sep 17]; Available from: Scholar
  41. 41.
    Vos BP, Maex R, Volny-Luraghi A, De Schutter E. Parallel fibers synchronize spontaneous activity in cerebellar Golgi cells. J Neurosci. 1999;19:RC6.PubMedGoogle Scholar
  42. 42.
    Catz N, Dicke PW, Thier P. Cerebellar complex spike firing is suitable to induce as well as to stabilize motor learning. Curr. Biol. [Internet]. 2005 [cited 2015 Jan 6];15:2179–89. Available from: Scholar
  43. 43.
    McDevitt CJ, Ebner TJ, Bloedel JR. The changes in Purkinje cell simple spike activity following spontaneous climbing fiber inputs. Brain Res. [Internet]. 1982 [cited 2015 Jan 6];237:484–91. Available from: Scholar
  44. 44.
    Hensbroek RA, Belton T, van Beugen BJ, Maruta J, Ruigrok TJH, Simpson JI. Identifying Purkinje cells using only their spontaneous simple spike activity. J. Neurosci. Methods [Internet]. 2014 [cited 2016 May 3];232:173–80. Available from: Scholar
  45. 45.
    Simpson JI, Hulscher HC, Sabel-Goedknegt E, Ruigrok TJH. Between in and out: linking morphology and physiology of cerebellar cortical interneurons. Prog. Brain Res. [Internet]. 2005 [cited 2015 Jan 6];148:329–40. Available from: Scholar
  46. 46.
    Ekerot CF, Jörntell H. Parallel fibre receptive fields of Purkinje cells and interneurons are climbing fibre-specific. Eur. J. Neurosci. [Internet]. 2001 [cited 2015 Jan 6];13:1303–10. Available from: Scholar
  47. 47.
    Jörntell H, Ekerot C-F. Reciprocal bidirectional plasticity of parallel fiber receptive fields in cerebellar Purkinje cells and their afferent interneurons. Neuron [Internet]. 2002 [cited 2015 Jan 6];34:797–806. Available from: Scholar
  48. 48.
    Armstrong DM, Rawson JA. Activity patterns of cerebellar cortical neurones and climbing fibre afferents in the awake cat. J. Physiol. [Internet]. 1979 [cited 2015 Jan 6];289:425–48. Available from:
  49. 49.
    Barmack NH, Yakhnitsa V. Functions of interneurons in mouse cerebellum. J. Neurosci. [Internet]. 2008 [cited 2014 Nov 27];28:1140–52. Available from: Scholar
  50. 50.
    Jörntell H, Ekerot C-F. Receptive field plasticity profoundly alters the cutaneous parallel fiber synaptic input to cerebellar interneurons in vivo. J. Neurosci. [Internet]. 2003 [cited 2015 Jan 6];23:9620–31. Available from: Scholar
  51. 51.
    Mann-Metzer P, Yarom Y. Pre- and postsynaptic inhibition mediated by GABA(B) receptors in cerebellar inhibitory interneurons. J. Neurophysiol. [Internet]. 2002 [cited 2015 Jan 6];87:183–90. Available from: Scholar
  52. 52.
    Blazquez PM, Yakusheva TA. GABA-A inhibition shapes the spatial and temporal response properties of Purkinje cells in the Macaque cerebellum. Cell Rep. [Internet]. 2015 [cited 2015 Sep 17];11:1043–53. Available from:
  53. 53.
    Heiney SA, Kim J, Augustine GJ, Medina JF. Precise control of movement kinematics by optogenetic inhibition of Purkinje cell activity. J. Neurosci. [Internet]. 2014 [cited 2015 Sep 17];34:2321–30. Available from:

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Ronit Givon-Mayo
    • 1
    • 2
    • 3
  • Shlomi Haar
    • 2
    • 4
    • 5
  • Yoav Aminov
    • 5
  • Esther Simons
    • 6
  • Opher Donchin
    • 2
    • 5
    • 6
    Email author
  1. 1.The Faculty of Health ScienceBen-Gurion University of the NegevBeer-ShevaIsrael
  2. 2.Zlotowski Center for NeuroscienceBen-Gurion University of the NegevBeer-ShevaIsrael
  3. 3.Physical Therapy DepartmentOno Academic CollegeKiryat OnoIsrael
  4. 4.Department of Brain and Cognitive SciencesBen-Gurion University of the NegevBeer-ShevaIsrael
  5. 5.Department of Biomedical EngineeringBen-Gurion University of the NegevBeer-ShevaIsrael
  6. 6.Department of NeuroscienceErasmus MCRotterdamThe Netherlands

Personalised recommendations