Skip to main content
Top
Published in: The Cerebellum 2/2017

01-04-2017 | Original Paper

Long Pauses in Cerebellar Interneurons in Anesthetized Animals

Authors: Ronit Givon-Mayo, Shlomi Haar, Yoav Aminov, Esther Simons, Opher Donchin

Published in: The Cerebellum | Issue 2/2017

Login to get access

Abstract

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.
Appendix
Available only for authorised users
Literature
3.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/15044532. 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​15044532.​
6.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/9331356 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​9331356
7.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/9169512 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​9169512
8.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/10024353 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​10024353
10.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/15339654 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​15339654
12.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/17522301 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​17522301
13.
15.
go back to reference De Schutter E, Steuber V. Patterns and pauses in Purkinje cell simple spike trains: experiments, modeling and theory. Neuroscience. 2009. p. 816–26. De Schutter E, Steuber V. Patterns and pauses in Purkinje cell simple spike trains: experiments, modeling and theory. Neuroscience. 2009. p. 816–26.
16.
go back to reference Person AL, Raman IM. Synchrony and neural coding in cerebellar circuits. Front. Neural Circuits [Internet]. 2012;6:97. Available from: http://journal.frontiersin.org/Journal/10.3389/fncir.2012.00097/abstract Person AL, Raman IM. Synchrony and neural coding in cerebellar circuits. Front. Neural Circuits [Internet]. 2012;6:97. Available from: http://​journal.​frontiersin.​org/​Journal/​10.​3389/​fncir.​2012.​00097/​abstract
18.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/10212289 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​10212289
19.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/19146818 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​19146818
21.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/15665875 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​15665875
22.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/16568098 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​16568098
25.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/18931886 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18931886
28.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/17493923 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​17493923
29.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/18952303 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18952303
32.
go back to reference Maex R, Steuber V. An integrator circuit in cerebellar cortex. Eur. J. Neurosci. [Internet]. 2013 [cited 2015 May 27];38:2917–32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23731348 Maex R, Steuber V. An integrator circuit in cerebellar cortex. Eur. J. Neurosci. [Internet]. 2013 [cited 2015 May 27];38:2917–32. Available from: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​23731348
34.
go back to reference 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.CrossRefPubMed 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.CrossRefPubMed
35.
go back to reference Lahti AC, Weiler MA, Michaelidis T, Parwani A, Tamminga CA. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology. 2001;25:455–67.CrossRefPubMed Lahti AC, Weiler MA, Michaelidis T, Parwani A, Tamminga CA. Effects of ketamine in normal and schizophrenic volunteers. Neuropsychopharmacology. 2001;25:455–67.CrossRefPubMed
39.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/3998798 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​3998798
40.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/26280650 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​26280650
41.
go back to reference Vos BP, Maex R, Volny-Luraghi A, De Schutter E. Parallel fibers synchronize spontaneous activity in cerebellar Golgi cells. J Neurosci. 1999;19:RC6.PubMed Vos BP, Maex R, Volny-Luraghi A, De Schutter E. Parallel fibers synchronize spontaneous activity in cerebellar Golgi cells. J Neurosci. 1999;19:RC6.PubMed
42.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/16360681 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​16360681
43.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/7083008 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​7083008
44.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/24880047 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​24880047
45.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/15661201 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​15661201
46.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/11298790 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​11298790
47.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/12062025 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​12062025
49.
go back to reference Barmack NH, Yakhnitsa V. Functions of interneurons in mouse cerebellum. J. Neurosci. [Internet]. 2008 [cited 2014 Nov 27];28:1140–52. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18234892 Barmack NH, Yakhnitsa V. Functions of interneurons in mouse cerebellum. J. Neurosci. [Internet]. 2008 [cited 2014 Nov 27];28:1140–52. Available from: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​18234892
50.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/14573542 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​14573542
51.
go back to reference 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: http://www.ncbi.nlm.nih.gov/pubmed/11784741 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: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​11784741
Metadata
Title
Long Pauses in Cerebellar Interneurons in Anesthetized Animals
Authors
Ronit Givon-Mayo
Shlomi Haar
Yoav Aminov
Esther Simons
Opher Donchin
Publication date
01-04-2017
Publisher
Springer US
Published in
The Cerebellum / Issue 2/2017
Print ISSN: 1473-4222
Electronic ISSN: 1473-4230
DOI
https://doi.org/10.1007/s12311-016-0792-y

Other articles of this Issue 2/2017

The Cerebellum 2/2017 Go to the issue