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Molecular Brain
Published in: Molecular Brain 1/2014

Open Access 01-12-2014 | Research

Essential role of axonal VGSC inactivation in time-dependent deceleration and unreliability of spike propagation at cerebellar Purkinje cells

Authors: Zhilai Yang, Erwei Gu, Xianfu Lu, Jin-Hui Wang

Published in: Molecular Brain | Issue 1/2014

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Abstract

Background

The output of the neuronal digital spikes is fulfilled by axonal propagation and synaptic transmission to influence postsynaptic cells. Similar to synaptic transmission, spike propagation on the axon is not secure, especially in cerebellar Purkinje cells whose spiking rate is high. The characteristics, mechanisms and physiological impacts of propagation deceleration and infidelity remain elusive. The spike propagation is presumably initiated by local currents that raise membrane potential to the threshold of activating voltage-gated sodium channels (VGSC).

Results

We have investigated the natures of spike propagation and the role of VGSCs in this process by recording spikes simultaneously on the somata and axonal terminals of Purkinje cells in cerebellar slices. The velocity and fidelity of spike propagation decreased during long-lasting spikes, to which the velocity change was more sensitive than fidelity change. These time-dependent deceleration and infidelity of spike propagation were improved by facilitating axonal VGSC reactivation, and worsen by intensifying VGSC inactivation.

Conclusion

Our studies indicate that the functional status of axonal VGSCs is essential to influencing the velocity and fidelity of spike propagation.
Appendix
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Literature
1.
Debanne D, Campanac E, Bialowas A, Carlier E, Alcaraz G: Axon physiology. Physiol Rev. 2011, 91: 555-602. 10.1152/physrev.00048.2009.PubMedCrossRef
2.
Kandel ER, Siegelbaum SA, Schwartz JH: Elementary interactions between neurons: synaptic transmission. Principles of neural science. Edited by: Kandel ER, Schwartz JH, Jessell TM. 2000, New York: McGraw-Hill, 175-308. 3
3.
Shepherd GM: Synaptic transmission. Neurobiology. Edited by: Shepherd GM. 1998, New York: Oxford University Press, 4
4.
Wang JH, Wei J, Chen X, Yu J, Chen N, Shi J: The gain and fidelity of transmission patterns at cortical excitatory unitary synapses improve spike encoding. J Cell Sci. 2008, 121: 2951-2960. 10.1242/jcs.025684.PubMedCrossRef
5.
Yu J, Qian H, Chen N, Wang JH: Quantal glutamate release is essential for reliable neuronal encodings in cerebral networks. PLoS ONE. 2011, 6: e25219-10.1371/journal.pone.0025219.PubMedPubMedCentralCrossRef
6.
Clark BA, Monsivais P, Branco T, London M, Hausser M: The site of action potential initiation in cerebellar Purkinje neurons. Nat Neurosci. 2005, 8: 137-139. 10.1038/nn1390.PubMedCrossRef
7.
Colbert CM, Pan E: Ion channel properties underlying axonal action potential initiation in pyramidal neurons. Nat Neurosci. 2002, 5: 533-538. 10.1038/nn0602-857.PubMedCrossRef
8.
9.
Davie JT, Clark BA, Hausser M: The origin of the complex spike in cerebellar Purkinje cells. J Neurosci. 2008, 28: 7599-7609. 10.1523/JNEUROSCI.0559-08.2008.PubMedPubMedCentralCrossRef
10.
11.
Hausser M, Stuart G, Racca C, Sakmann B: Axonal initiation and active dendritic propagation of action potentials in substantia nigra neurons. Neuron. 1995, 15: 637-647. 10.1016/0896-6273(95)90152-3.PubMedCrossRef
12.
Hu W, Tian C, Li T, Yang P, Hou H, Shu YS: Distinct contribution of Nav1.6 and Nav1.2 in action potential initiation and backpropagation. Nat Neurosci. 2009, 12: 996-1002. 10.1038/nn.2359.PubMedCrossRef
13.
Kang Y, Saito M, Sato H, Toyoda H, Maeda Y, Hirai T, Bae YC: Involvement of persistent Na + current in spike initiation in primary sensory neurons of the rat mesencephalic trigeminal nucleus. J Neurophysiol. 2007, 97: 2385-2393. 10.1152/jn.01191.2006.PubMedCrossRef
14.
Kole MHP, Ilschner SU, Kampa BM, Williams SR, Ruben PC, Stuart GJ: Action potential generation requires a high sodium channel density in the axon initial segment. Nat Neurosci. 2008, 11: 178-186. 10.1038/nn2040.PubMedCrossRef
15.
Kuba H, Ishii TM, Ohmori H: Axonal site of spike initiation enhances auditory coincidence detection. Nature. 2006, 444: 1069-1072. 10.1038/nature05347.PubMedCrossRef
16.
Maarten H, Kole P, Stuart GJ: Is action potential threshold lowest in the axon?. Nat Neurosci. 2008, 11: 1253-1255. 10.1038/nn.2203.CrossRef
17.
Meeks JP, Mennerick S: Action potential initiation and propagation in CA3 pyramidal axons. J Neurophysiol. 2007, 97: 3460-3472. 10.1152/jn.01288.2006.PubMedCrossRef
18.
Palmer LM, Clark BA, Grundemann J, Roth A, Stuart GJ, Hausser M: Initiation of simple and complex spikes in cerebellar Purkinje cells. J Physiol. 2010, 588: 1709-1717. 10.1113/jphysiol.2010.188300.PubMedPubMedCentralCrossRef
19.
Chen N, Yu J, Qian H, Ge R, Wang JH: Axons amplify somatic incomplete spikes into uniform amplitudes in mouse cortical pyramidal neurons. PLoS ONE. 2010, 5 (7): e11868-10.1371/journal.pone.0011868.PubMedPubMedCentralCrossRef
20.
Engel D, Jonas P: Presynaptic action potential amplification by voltage-gated Na + channels in hippocampal mossy fiber boutons. Neuron. 2005, 45: 405-417. 10.1016/j.neuron.2004.12.048.PubMedCrossRef
21.
Hodgkin AL, Huxley AF: Propagation of electrical signals along giant nerve fibers. Proc R Soc Lond B Biol Sci. 1952, 140: 177-183. 10.1098/rspb.1952.0054.PubMedCrossRef
22.
23.
Khaliq ZM, Raman IM: Axonal propagation of simple and complex spikes in cerebellar Purkinje neurons. J Neurosci. 2005, 25: 454-463. 10.1523/JNEUROSCI.3045-04.2005.PubMedCrossRef
24.
Monsivais P, Clark BA, Roth A, Hausser M: Determinants of action potential propagation in cerebellar Purkinje cell axons. J Neurosci. 2005, 25: 464-472. 10.1523/JNEUROSCI.3871-04.2005.PubMedCrossRef
25.
Bucher D, Goaillard JM: Beyond faithful conduction: short-term dynamics, neuromodulation, and long-term regulation of spike propagation in the axon. Prog Neurobiol. 2011, 94: 307-346. 10.1016/j.pneurobio.2011.06.001.PubMedPubMedCentralCrossRef
26.
Debanne D, Guerineau NC, Gahwiler BH, Thompson SM: Action-potential propagation gated by an axonal I (A)-like K + conductance in hippocampus. Nature. 1997, 389: 286-289. 10.1038/38502.PubMedCrossRef
27.
Khaliq ZM, Raman IM: Relative contributions of axonal and somatic Na channels to action potential initiation in cerebellar Purkinje neurons. J Neurosci. 2006, 26: 1935-1944. 10.1523/JNEUROSCI.4664-05.2006.PubMedCrossRef
28.
Meeks JP, Mennerick S: Selective effects of potassium elevations on glutamate signaling and action potential conduction in hippocampus. J Neurosci. 2004, 24: 197-206. 10.1523/JNEUROSCI.4845-03.2004.PubMedCrossRef
29.
Debanne D: Information processing in the axon. Nat Rev Neurosci. 2004, 5: 304-316. 10.1038/nrn1397.PubMedCrossRef
30.
Eccles JC, Sasaki K, Strata P: Interpretation of the potential fields generated in the cerebellar cortex by a mossy fibre volley. Exp Brain Res. 1967, 3: 58-80.PubMed
31.
Harvey RJ, Porter R, Rawson JA: The natural discharges of Purkinje cells in paravermal regions of lobules V and VI of the monkey’s cerebellum. J Physiol. 1977, 271: 515-536.PubMedPubMedCentralCrossRef
32.
33.
Aldrich RW, Corey DP, Stevens CF: A reinterpretation of mammalian sodium channel gating based on single channel recording. Nature. 1983, 306: 436-441. 10.1038/306436a0.PubMedCrossRef
34.
Chen N, Chen X, Yu J, Wang J-H: After-hyperpolarization improves spike programming through lowering threshold potentials and refractory periods mediated by voltage-gated sodium channels. Biochem Biophys Res Commun. 2006, 346: 938-945. 10.1016/j.bbrc.2006.06.003.PubMedCrossRef
35.
Goldman L: Stationarity of sodium channel gating kinetics in excised patches from neuroblastoma N1E 115. Biophysics Journal. 1995, 69: 2364-2368. 10.1016/S0006-3495(95)80105-0.CrossRef
36.
Ge R, Qian H, Wang JH: Physiological synaptic signals initiate sequential spikes at soma of cortical pyramidal neurons. Mol Brain. 2011, 4: 19-10.1186/1756-6606-4-19.PubMedPubMedCentralCrossRef
37.
Deqenetais E, Thierry AM, Glowinski J, Gioanni Y: Electrophysiological properties of pyramidal neurons in the rat prefrontal cortex: an in vivo intracellular recording study. Cereb Cortex. 2002, 12: 1-16. 10.1093/cercor/12.1.1.CrossRef
38.
Haider B, Duque A, Hasenstaub A, McCormick DA: Neocortical network activity in vivo is generated through a dynamic balance of excitation and inhibition. J Neurosci. 2006, 26: 4535-4545. 10.1523/JNEUROSCI.5297-05.2006.PubMedCrossRef
39.
Henze DA, Buzsaki G: Action potential threshold of hippocampal pyramidal cells in vivo is increased by recent spiking activity. Neuroscience. 2001, 105: 121-130. 10.1016/S0306-4522(01)00167-1.PubMedCrossRef
40.
Zhang Z, Yu YQ, Liu CH, Chan YS, He J: Reprint of “frequency tuning and firing pattern properties of auditory thalamic neurons: an in vivo intracellular recording from the guinea pig”. Neuroscience. 2008, 154: 273-282. 10.1016/S0306-4522(08)00741-0.PubMedCrossRef
41.
Chen N, Chen SL, Wu YL, Wang JH: The refractory periods and threshold potentials of sequential spikes measured by whole-cell recordings. Biochem Biophys Res Commun. 2006, 340: 151-157. 10.1016/j.bbrc.2005.11.170.PubMedCrossRef
42.
Chen N, Zhu Y, Gao X, Guan S, Wang J-H: Sodium channel-mediated intrinsic mechanisms underlying the differences of spike programming among GABAergic neurons. Biochem Biophys Res Commun. 2006, 346: 281-287. 10.1016/j.bbrc.2006.05.120.PubMedCrossRef
43.
Jaeger D, Bower JM: Prolonged responses in rat cerebellar Purkinje cells following activation of the granule cell layer: an intracellular in vitro and in vivo investigation. Exp Brain Res. 1994, 100: 200-214.PubMedCrossRef
44.
Loewenstein Y, Mahon S, Chadderton P, Kitamura K, Sompolinsky H, Yarom Y, Hausser M: Bistability of cerebellar Purkinje cells modulated by sensory stimulation. Nat Neurosci. 2005, 8: 202-211. 10.1038/nn1393.PubMedCrossRef
45.
Mantegazza M, Franceschetti S, Avanzini G: Anemone toxin (ATX II)-induced increase in persistent sodium current: effects on the firing properties of rat neocortical pyramidal neurones. J Physiol. 1998, 507 (Pt 1): 105-116.PubMedPubMedCentralCrossRef
46.
Rathmayer W: Anemone toxin discriminates between ionic channels for receptor potential and for action potential production in a sensory neuron. Neurosci Lett. 1979, 13: 313-318. 10.1016/0304-3940(79)91512-X.PubMedCrossRef
47.
Berecki G, Wilders R, de Jonge B, van Ginneken AC, Verkerk AO: Re-evaluation of the action potential upstroke velocity as a measure of the Na + current in cardiac myocytes at physiological conditions. PLoS ONE. 2010, 5: e15772-10.1371/journal.pone.0015772.PubMedPubMedCentralCrossRef
48.
Remme CA, Verkerk AO, Nuyens D, van Ginneken AC, van Brunschot S, Belterman CN, Wilders R, van Roon MA, Tan HL, Wilde AA, et al: Overlap syndrome of cardiac sodium channel disease in mice carrying the equivalent mutation of human SCN5A-1795insD. Circulation. 2006, 114: 2584-2594. 10.1161/CIRCULATIONAHA.106.653949.PubMedCrossRef
49.
D’Angelo E, Mazzarello P, Prestori F, Mapelli J, Solinas S, Lombardo P, Cesana E, Gandolfi D, Congi L: The cerebellar network: from structure to function and dynamics. Brain Res Rev. 2011, 66: 5-15. 10.1016/j.brainresrev.2010.10.002.PubMedCrossRef
50.
Foust A, Popovic M, Zecevic D, McCormick DA: Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar Purkinje neurons. J Neurosci. 2010, 30: 6891-6902. 10.1523/JNEUROSCI.0552-10.2010.PubMedPubMedCentralCrossRef
51.
Sugihara I, Fujita H, Na J, Quy PN, Li BY, Ikeda D: Projection of reconstructed single Purkinje cell axons in relation to the cortical and nuclear aldolase C compartments of the rat cerebellum. J Comp Neurol. 2009, 512: 282-304. 10.1002/cne.21889.PubMedCrossRef
52.
Wang DJ, Yang D, Su LD, Xie YJ, Zhou L, Sun CL, Wang Y, Wang XX, Shen Y: Cytosolic phospholipase A2 alpha/arachidonic acid signaling mediates depolarization-induced suppression of excitation in the cerebellum. PLoS ONE. 2012, 7: e41499-10.1371/journal.pone.0041499.PubMedPubMedCentralCrossRef
53.
Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silbergerg G, Wu C: Interneurons of the neocortical inhibitory system. Nature Review of Neuroscience. 2004, 5: 793-807. 10.1038/nrn1519.CrossRef
54.
Plazas PV, Nicol X, Spitzer NC: Activity-dependent competition regulates motor neuron axon pathfinding via PlexinA3. Proc Natl Acad Sci U S A. 2013, 110: 1524-1529. 10.1073/pnas.1213048110.PubMedPubMedCentralCrossRef
55.
Uusisaari M, Knopfel T: Functional classification of neurons in the mouse lateral cerebellar nuclei. Cerebellum. 2011, 10: 637-646. 10.1007/s12311-010-0240-3.PubMedPubMedCentralCrossRef
56.
Wang JH, Yang Z, Qian H, Chen N: Functional compatibility between Purkinje cell axon branches and their target neurons in the cerebellum. Biophys J. 2013, 104: 330a-CrossRef
57.
Chen N, Chen X, Wang J-H: Homeostasis established by coordination of subcellular compartment plasticity improves spike encoding. J Cell Sci. 2008, 121: 2961-2971. 10.1242/jcs.022368.PubMedCrossRef
58.
Caldwell JH, Schaller KL, Lasher RS, Peles E, Levinson SR: Sodium channel Na (v)1.6 is localized at nodes of ranvier, dendrites, and synapses. Proc Natl Acad Sci U S A. 2000, 97: 5616-5620. 10.1073/pnas.090034797.PubMedPubMedCentralCrossRef
59.
Carter BC, Bean BP: Incomplete inactivation and rapid recovery of voltage-dependent sodium channels during high-frequency firing in cerebellar Purkinje neurons. J Neurophysiol. 2011, 105: 860-871. 10.1152/jn.01056.2010.PubMedPubMedCentralCrossRef
60.
Garrido JJ, Fernandes F, Moussif A, Fache MP, Giraud P, Dargent B: Dynamic compartmentalization of the voltage-gated sodium channels in axons. Biol Cell. 2003, 95: 437-445. 10.1016/S0248-4900(03)00091-1.PubMedCrossRef
61.
Schaller KL, Caldwell JH: Expression and distribution of voltage-gated sodium channels in the cerebellum. Cerebellum. 2003, 2: 2-9. 10.1080/14734220309424.PubMedCrossRef
62.
Waxman SG, Cummins TR, Black JA, Dib-Hajj S: Diverse functions and dynamic expression of neuronal sodium channels. Novartis Found Symp. 2002, 241: 34-60.PubMedCrossRef
63.
Wang JH, Kelly PT: Postsynaptic injection of Ca2+/CaM induces synaptic potentiation requiring CaM-KII and PKC activity. Neuron. 1995, 15: 443-452. 10.1016/0896-6273(95)90048-9.PubMedCrossRef
64.
Wang J-H, Kelly PT: Balance between postsynaptic Ca2 + −dependent protein kinase and phosphatase activities controlling synaptic strength. Learn Mem. 1996, 3: 170-181. 10.1101/lm.3.2-3.170.PubMedCrossRef
65.
Wang J-H, Kelly PT: Postsynaptic calcineurin activity down-regulates synaptic transmission by weakening intracellular Ca2+ signaling mechanisms in hippocampal CA1 neurons. J Neurosci. 1997, 17: 4600-4611.PubMed
66.
Zhang M, Hung F, Zhu Y, Xie Z, Wang J: Calcium signal-dependent plasticity of neuronal excitability developed postnatally. J Neurobiol. 2004, 61: 277-287. 10.1002/neu.20045.PubMedCrossRef
67.
Mackenzie PJ, Umemiya M, Murphy TH: Ca2+ imaging of CNS axons in culture indicates reliable coupling between single action potentials and distal functional release sites. Neuron. 1996, 16: 783-795. 10.1016/S0896-6273(00)80098-7.PubMedCrossRef
68.
Ge R, Chen N, Wang JH: Real-time neuronal homeostasis by coordinating VGSC intrinsic properties. Biochem Biophys Res Commun. 2009, 387: 585-589. 10.1016/j.bbrc.2009.07.066.PubMedCrossRef
69.
Wang J-H: Short-term cerebral ischemia causes the dysfunction of interneurons and more excitation of pyramidal neurons. Brain Res Bull. 2003, 60: 53-58. 10.1016/S0361-9230(03)00026-1.PubMedCrossRef
70.
Yu J, Qian H, Wang JH: Upregulation of transmitter release probability improves a conversion of synaptic analogue signals into neuronal digital spikes. Mol Brain. 2012, 5: 26-10.1186/1756-6606-5-26.PubMedPubMedCentralCrossRef
71.
Hockberger PE, Tseng H-Y, Connor JA: Development of rat cerebellar purkinje cells: electrophysiological properties following acute isolation and in long-term culture. J Neurosci. 1989, 9: 2258-2271.PubMed
72.
73.
Qi Y, Huang L, Ni H, Zhou X, Zhang J, Zhu Y, Ge M, Guan S, Wang JH: Intracellular Ca2+ regulates spike encoding at cortical GABAergic neurons and cerebellar Purkinje cells differently. Biochem Biophys Res Commun. 2009, 381: 129-133. 10.1016/j.bbrc.2009.02.058.PubMedCrossRef
74.
Stuart G, Hausser M: Initiation and spread of sodium action potentials in cerebellar Purkinje cells. Neuron. 1994, 13: 703-712. 10.1016/0896-6273(94)90037-X.PubMedCrossRef
75.
Wang JH, Zhang M: Differential modulation of glutamatergic and cholinergic synapses by calcineurin in hippocampal CA1 fast-spiking interneurons. Brain Res. 1004: 125-135.
76.
Kress GJ, Dowling MJ, Meeks JP, Mennerick S: High threshold, proximal initiation, and slow conduction velocity of action potentials in dentate granule neuron mossy fibers. J Neurophysiol. 2008, 100: 281-291. 10.1152/jn.90295.2008.PubMedPubMedCentralCrossRef
77.
Wang J-H, Kelly PT: Ca2+/CaM signalling pathway up-regulates glutamatergic synaptic function in non-pyramidal fast-spiking neurons of hippocampal CA1. J Physiol Lond. 2001, 533: 407-422. 10.1111/j.1469-7793.2001.0407a.x.PubMedPubMedCentralCrossRef
Metadata
Title
Essential role of axonal VGSC inactivation in time-dependent deceleration and unreliability of spike propagation at cerebellar Purkinje cells
Authors
Zhilai Yang
Erwei Gu
Xianfu Lu
Jin-Hui Wang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Brain / Issue 1/2014
Electronic ISSN: 1756-6606
DOI
https://doi.org/10.1186/1756-6606-7-1

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