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The Cerebellum

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01.10.2013 | Original Paper

Gain Control of Synaptic Response Function in Cerebellar Nuclear Neurons by a Calcium-Activated Potassium Conductance

verfasst von: Steven Si Feng, Risa Lin, Volker Gauck, Dieter Jaeger

Erschienen in: The Cerebellum | Ausgabe 5/2013

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Abstract

Small conductance Ca²⁺-activated potassium (SK) current provides an important modulator of excitatory synaptic transmission, which undergoes plastic regulation via multiple mechanisms. We examined whether inhibitory input processing is also dependent on SK current in the cerebellar nuclei (CN) where inhibition provides the only route of information transfer from the cerebellar cortical Purkinje cells. We employed dynamic clamping in conjunction with computer simulations to address this question. We found that SK current plays a critical role in the inhibitory synaptic control of spiking output. Specifically, regulation of SK current density resulted in a gain control of spiking output, such that low SK current promoted large output signaling for large inhibitory cell input fluctuations due to Purkinje cell synchronization. In contrast, smaller nonsynchronized Purkinje cell input fluctuations were not amplified. Regulation of SK density in the CN therefore would likely lead to important consequences for the transmission of synchronized Purkinje cell activity to the motor system.

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Palkovits M, Mezey E, Hamori J, Szentagothai J. Quantitative histological analysis of the cerebellar nuclei in the cat. I. Numerical data on cells and synapses. Exp Brain Res. 1977;28:189–209.PubMed

Jaeger D. Mini-review: synaptic integration in the cerebellar nuclei—perspectives from dynamic clamp and computer simulation studies. Cerebellum. 2011;10:659–66.PubMedCrossRef

Walter JT, Khodakhah K. The linear computational algorithm of cerebellar Purkinje cells. J Neurosci. 2006;26:12861–72.PubMedCrossRef

Walter JT, Khodakhah K. The advantages of linear information processing for cerebellar computation. Proc Natl Acad Sci U S A. 2009;106:4471–6.PubMedCrossRef

Gauck V, Jaeger D. The control of rate and timing of spikes in the deep cerebellar nuclei by inhibition. J Neurosci. 2000;20:3006–16.PubMed

De Zeeuw CI, Hoebeek FE, Bosman LWJ, Schonewille M, Witter L, Koekkoek SK. Spatiotemporal firing patterns in the cerebellum. Nat Rev Neurosci. 2011;12:327–44.PubMedCrossRef

Shin SL, De Schutter E. Dynamic synchronization of Purkinje cell simple spikes. J Neurophysiol. 2006;96:3485–91.PubMedCrossRef

Jahnsen H. Electrophysiological characteristics of neurones in the guinea-pig deep cerebellar nuclei in vitro. J Physiol. 1986;372:129–47.PubMed

Uusisaari M, Obata K, Knopfel T. Morphological and electrophysiological properties of GABAergic and non-GABAergic cells in the deep cerebellar nuclei. J Neurophysiol. 2007;97:901–11.PubMedCrossRef

10.

Molineux ML, Mehaffey WH, Tadayonnejad R, Anderson D, Tennent AF, Turner RW. Ionic factors governing rebound burst phenotype in rat deep cerebellar neurons. J Neurophysiol. 2008;100:2684–701.PubMedCrossRef

11.

Molineux ML, McRory JE, McKay BE, Hamid J, Mehaffey WH, Rehak R, et al. Specific t-type calcium channel isoforms are associated with distinct burst phenotypes in deep cerebellar nuclear neurons. Proc Natl Acad Sci U S A. 2006;103:5555–60.PubMedCrossRef

12.

Alvina K, Ellis-Davies G, Khodakhah K. T-type calcium channels mediate rebound firing in intact deep cerebellar neurons. Neuroscience. 2009;158:635–41.PubMedCrossRef

13.

Sangrey T, Jaeger D. Multiple components of rebound spiking in deep cerebellar nucleus neurons. Eur J Neurosci. 2010;32:1646–57.PubMedCrossRef

14.

Hoebeek FE, Witter L, Ruigrok TJ, De Zeeuw CI. Differential olivo-cerebellar cortical control of rebound activity in the cerebellar nuclei. Proc Natl Acad Sci U S A. 2010;107:8410–5.PubMedCrossRef

15.

Bengtsson F, Ekerot CF, Jorntell H. In vivo analysis of inhibitory synaptic inputs and rebounds in deep cerebellar nuclear neurons. PLoS One. 2011;6:e18822.

16.

Lang EJ, Sugihara I, Welsh JP, Llinas R. Patterns of spontaneous Purkinje cell complex spike activity in the awake rat. J Neurosci. 1999;19:2728–39.PubMed

17.

Schultz SR, Kitamura K, Post-Uiterweer A, Krupic J, Hausser M. Spatial pattern coding of sensory information by climbing fiber-evoked calcium signals in networks of neighboring cerebellar Purkinje cells. J Neurosci. 2009;29:8005–15.PubMedCrossRef

18.

Ozden I, Sullivan MR, Lee HM, Wang SSH. Reliable coding emerges from coactivation of climbing fibers in microbands of cerebellar purkinje neurons. J Neurosci. 2009;29:10463–73.PubMedCrossRef

19.

Aizenman CD, Linden DJ. Regulation of the rebound depolarization and spontaneous firing patterns of deep nuclear neurons in slices of rat cerebellum. J Neurophysiol. 1999;82:1697–709.PubMed

20.

Raman IM, Gustafson AE, Padgett D. Ionic currents and spontaneous firing in neurons isolated from the cerebellar nuclei. J Neurosci. 2000;20:9004–16.PubMed

21.

Magee JC. Dendritic hyperpolarization-activated currents modify the integrative properties of hippocampal ca1 pyramidal neurons. J Neurosci. 1998;18:7613–24.PubMed

22.

Chan CS, Shigemoto R, Mercer JN, Surmeier DJ. HCN2 and HCN1 channels govern the regularity of autonomous pacemaking and synaptic resetting in globus pallidus neurons. J Neurosci. 2004;24:9921–32.PubMedCrossRef

23.

Wolfart J, Roeper J. Selective coupling of t-type calcium channels to SK potassium channels prevents intrinsic bursting in dopaminergic midbrain neurons. J Neurosci. 2002;22:3404–13.PubMed

24.

Deister CA, Chan CS, Surmeier DJ, Wilson CJ. Calcium-activated SK channels influence voltage-gated ion channels to determine the precision of firing in globus pallidus neurons. J Neurosci. 2009;29:8452–61.PubMedCrossRef

25.

Canavier CC, Landry RS. An increase in AMPA and a decrease in SK conductance increase burst firing by different mechanisms in a model of a dopamine neuron in vivo. J Neurophysiol. 2006;96:2549–63.PubMedCrossRef

26.

Gauck V, Jaeger D. The contribution of NMDA and AMPA conductances to the control of spiking in neurons of the deep cerebellar nuclei. J Neurosci. 2003;23:8109–18.PubMed

27.

Person AL, Raman IM. Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei. Nature. 2012;481:502–6.CrossRef

28.

Pugh JR, Raman IM. GABAA receptor kinetics in the cerebellar nuclei: evidence for detection of transmitter from distant release sites. Biophys J. 2005;88:1740–54.PubMedCrossRef

29.

Anchisi D, Scelfo B, Tempia F. Postsynaptic currents in deep cerebellar nuclei. J Neurophysiol. 2001;85:323–31.PubMed

30.

Steuber V, Schultheiss NW, Silver RA, De Schutter E, Jaeger D. Determinants of synaptic integration and heterogeneity in rebound firing explored with data driven models of deep cerebellar nucleus cells. J Comput Neurosci. 2011;30:633–58.PubMedCrossRef

31.

Steuber V, De Schutter E, Jaeger D. Passive models of neurons in the deep cerebellar nuclei: the effect of reconstruction errors. Neurocomputing. 2004;58–60:563–8.CrossRef

32.

Jahnsen H. Extracellular activation and membrane conductances of neurones in the guinea-pig deep cerebellar nuclei in vitro. J Physiol. 1986;372:149–68.PubMed

33.

Llinas R, Muhlethaler M. Electrophysiology of guinea-pig cerebellar nuclear cells in the in vitro brain stem-cerebellar preparation. J Physiol. 1988;404:241–58.PubMed

34.

Bower J, Beeman D. The book of genesis. New York: Springer; 1997.

35.

Lin RJ, Jaeger D. Using computer simulations to determine the limitations of dynamic clamp stimuli applied at the soma in mimicking distributed conductance sources. J Neurophysiol. 2011;105:2610–24.PubMedCrossRef

36.

Feng S, Jaeger D. The role of SK calcium-dependent potassium currents in regulating the activity of deep cerebellar nucleus neurons: a dynamic clamp study. Cerebellum. 2008;7:542–6.PubMedCrossRef

37.

Bennett BD, Callaway JC, Wilson CJ. Intrinsic membrane properties underlying spontaneous tonic firing in neostriatal cholinergic interneurons. J Neurosci. 2000;20:8493–503.PubMed

38.

Nedergaard S, Flatman JA, Engberg I. Nifedipine-conotoxin-sensitive and omega-conotoxin-sensitive Ca²⁺ conductances in guinea-pig substantia nigra-pars-compacta neurons. J Physiol Lond. 1993;466:727–47.PubMed

39.

De Waele C, Serafin M, Khateb A, Yabe T, Vidal PP, Muhlethaler M. Medial vestibular nucleus in the guinea-pig—apamin-induced rhythmic burst firing—an in-vitro and in-vivo study. Exp Brain Res. 1993;95:213–22.PubMedCrossRef

40.

McKay BE, McRory JE, Molineux ML, Hamid J, Snutch TP, Zamponi GW, et al. Ca(v)3 t-type calcium channel isoforms differentially distribute to somatic and dendritic compartments in rat central neurons. Eur J Neurosci. 2006;24:2581–94.PubMedCrossRef

41.

Alvina K, Khodakhah K. Selective regulation of spontaneous activity of neurons of the deep cerebellar nuclei by n-type calcium channels in juvenile rats. J Physiol Lond. 2008;586:2523–38.PubMedCrossRef

42.

Giessel AJ, Sabatini BL. M1 muscarinic receptors boost synaptic potentials and calcium influx in dendritic spines by inhibiting postsynaptic SK channels. Neuron. 2010;68:936–47.PubMedCrossRef

43.

Maylie J, Adelman JP. Cholinergic signaling through synaptic SK channels: it's a protein kinase but which one? Neuron. 2010;68:809–11.PubMedCrossRef

44.

Womack MD, Chevez C, Khodakhah K. Calcium-activated potassium channels are selectively coupled to p/q-type calcium channels in cerebellar purkinje neurons. J Neurosci. 2004;24:8818–22.PubMedCrossRef

45.

Hosy E, Piochon C, Teuling E, Rinaldo L, Hansel C. SK2 channel expression and function in cerebellar Purkinje cells. J Physiol Lond. 2011;589:3433–40.PubMedCrossRef

46.

Belmeguenai A, Hosy E, Bengtsson F, Pedroarena CM, Piochon C, Teuling E, et al. Intrinsic plasticity complements long-term potentiation in parallel fiber input gain control in cerebellar Purkinje cells. J Neurosci. 2010;30:13630–43.PubMedCrossRef

47.

Schonewille M, Belmeguenai A, Koekkoek SK, Houtman SH, Boele HJ, van Beugen BJ, et al. Purkinje cell-specific knockout of the protein phosphatase PP2B impairs potentiation and cerebellar motor learning. Neuron. 2010;67:618–28.PubMedCrossRef

48.

Bond CT, Herson PS, Strassmaier T, Hammond R, Stackman R, Maylie J, et al. Small conductance Ca²⁺-activated k⁺ channel knock-out mice reveal the identity of calcium-dependent afterhyperpolarization currents. J Neurosci. 2004;24:5301–6.PubMedCrossRef

49.

Bond CT, Maylie J, Adelman JP. Sk channels in excitability, pacemaking and synaptic integration. Curr Opin Neurobiol. 2005;15:305–11.PubMedCrossRef

50.

De Schutter E, Steuber V. Patterns and pauses in Purkinje cell simple spike trains: experiments, modeling and theory. Neuroscience. 2009;162:816–26.PubMedCrossRef

51.

Destexhe A, Pare D. Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo. J Neurophysiol. 1999;81:1531–47.PubMed

52.

Destexhe A, Rudolph M, Fellous JM, Sejnowski TJ. Fluctuating synaptic conductances recreate in vivo-like activity in neocortical neurons. Neuroscience. 2001;107:13–24.PubMedCrossRef

53.

Alvina K, Walter JT, Kohn A, Ellis-Davies G, Khodakhah K. Questioning the role of rebound firing in the cerebellum. Nat Neurosci. 2008;11:1256–8.PubMedCrossRef

54.

Tadayonnejad R, Anderson D, Molineux ML, Mehaffey WH, Jayasuriya K, Turner RW. Rebound discharge in deep cerebellar nuclear neurons in vitro. Cerebellum. 2010;9:352–74.PubMedCrossRef

55.

Tadayonnejad R, Mehaffey WH, Anderson D, Turner RW. Reliability of triggering postinhibitory rebound bursts in deep cerebellar neurons. Channels (Austin). 2009;3:149–55.CrossRef

56.

Medina JF, Lisberger SG. Encoding and decoding of learned smooth-pursuit eye movements in the floccular complex of the monkey cerebellum. J Neurophysiol. 2009;102:2039–54.PubMedCrossRef

57.

Cao Y, Maran SK, Dhamala M, Jaeger D, Heck DH. Behavior-related pauses in simple-spike activity of mouse Purkinje cells are linked to spike rate modulation. J Neurosci. 2012;32:8678–85.PubMedCrossRef

58.

Sourdet V, Russier M, Daoudal G, Ankri N, Debanne D. Long-term enhancement of neuronal excitability and temporal fidelity mediated by metabotropic glutamate receptor subtype 5. J Neurosci. 2003;23:10238–48.PubMed

59.

Turrigiano GG, Nelson SB. Hebb and homeostasis in neuronal plasticity. Curr Opin Neurobiol. 2000;10:358–64.PubMedCrossRef

60.

Marder E, Prinz AA. Current compensation in neuronal homeostasis. Neuron. 2003;37:2–4.PubMedCrossRef

61.

Brickley SG, Revilla V, Cull-Candy SG, Wisden W, Farrant M. Adaptive regulation of neuronal excitability by a voltage-independent potassium conductance. Nature. 2001;409:88–92.PubMedCrossRef

62.

Pedroarena C. BK and KV3.1 potassium channels control different aspects of deep cerebellar nuclear neurons action potentials and spiking activity. Cerebellum. 2011;10:647–58.PubMedCrossRef

63.

Euler T, Denk W. Dendritic processing. Curr Opin Neurobiol. 2001;11:415–22.PubMedCrossRef

64.

Eilers J, Konnerth A. Dendritic signal integration [review] [55 refs]. Curr Opin Neurobiol. 1997;7:385–90.PubMedCrossRef

65.

Johnston D, Magee JC, Colbert CM, Christie BR. Active properties of neuronal dendrites. Annu Rev Neurosci. 1996;19:165–86.PubMedCrossRef

66.

London M, Hausser M. Dendritic computation. Annu Rev Neurosci. 2005;28:503–32.PubMedCrossRef

67.

Beck H, Yaari Y. Plasticity of intrinsic neuronal properties in CNS disorders. Nat Rev Neurosci. 2008;9:357–69.PubMedCrossRef

68.

Hoebeek FE, Stahl JS, van Alphen AM, Schonewille M, Luo C, Rutteman M, et al. Increased noise level of Purkinje cell activities minimizes impact of their modulation during sensorimotor control. Neuron. 2005;45:953–65.PubMedCrossRef

69.

Levin SI, Khaliq ZM, Aman TK, Grieco TM, Kearney JA, Raman IM, et al. Impaired motor function in mice with cell-specific knockout of sodium channel Scn8A (Na(v)1.6) in cerebellar Purkinje neurons and granule cells. J Neurophysiol. 2006;96:785–93.PubMedCrossRef

70.

Sausbier M, Hu H, Arntz C, Feil S, Kamm S, Adelsberger H, et al. Cerebellar ataxia and Purkinje cell dysfunction caused by Ca²⁺-activated k⁺ channel deficiency. Proc Natl Acad Sci U S A. 2004;101:9474–8.PubMedCrossRef

71.

Cheron G, Sausbier M, Sausbier U, Neuhuber W, Ruth P, Dan B, Servais L. BK channels control cerebellar purkinje and golgi cell rhythmicity in vivo. Plos One. 2009;4:e7991.

72.

Calderon DP, Fremont R, Kraenzlin F, Khodakhah K. The neural substrates of rapid-onset dystonia-parkinsonism. Nat Neurosci. 2011;14:357–65.PubMedCrossRef

73.

Jinnah HA, Hess EJ, LeDoux MS, Sharma N, Baxter MG, DeLong MR. Rodent models for dystonia research: characteristics, evaluation, and utility. Mov Disord. 2005;20:283–92.PubMedCrossRef

74.

LeDoux MS, Lorden JF. Abnormal spontaneous and harmaline-stimulated Purkinje cell activity in the awake genetically dystonic rat. Exp Brain Res. 2002;145:457–67.PubMedCrossRef

75.

LeDoux MS. Animal models of dystonia: lessons from a mutant rat. Neurobiol Dis. 2011;42:152–61.PubMedCrossRef

76.

Walter JT, Alvina K, Womack MD, Chevez C, Khodakhah K. Decreases in the precision of Purkinje cell pacemaking cause cerebellar dysfunction and ataxia. Nat Neurosci. 2006;9:389–97.PubMedCrossRef

77.

Alvina K, Khodakhah K. The therapeutic mode of action of 4-aminopyridine in cerebellar ataxia. J Neurosci. 2010;30:7258–68.PubMedCrossRef

Titel: Gain Control of Synaptic Response Function in Cerebellar Nuclear Neurons by a Calcium-Activated Potassium Conductance
verfasst von: Steven Si Feng
Risa Lin
Volker Gauck
Dieter Jaeger
Publikationsdatum: 01.10.2013
Verlag: Springer US
Erschienen in: The Cerebellum / Ausgabe 5/2013
Print ISSN: 1473-4222
Elektronische ISSN: 1473-4230
DOI: https://doi.org/10.1007/s12311-013-0476-9

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