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Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei

Abstract

An unusual feature of the cerebellar cortex is that its output neurons, Purkinje cells, release GABA (γ-aminobutyric acid). Their high intrinsic firing rates1 (50 Hz) and extensive convergence2,3 predict that their target neurons in the cerebellar nuclei would be largely inhibited unless Purkinje cells pause their spiking, yet Purkinje and nuclear neuron firing rates do not always vary inversely4. One indication of how these synapses transmit information is that populations of Purkinje neurons synchronize their spikes during cerebellar behaviours5,6,7,8,9,10,11. If nuclear neurons respond to Purkinje synchrony, they may encode signals from subsets of inhibitory inputs7,12,13,14. Here we show in weanling and adult mice that nuclear neurons transmit the timing of synchronous Purkinje afferent spikes, owing to modest Purkinje-to-nuclear convergence ratios (40:1), fast inhibitory postsynaptic current kinetics (τdecay = 2.5 ms) and high intrinsic firing rates (90 Hz). In vitro, dynamically clamped asynchronous inhibitory postsynaptic potentials mimicking Purkinje afferents suppress nuclear cell spiking, whereas synchronous inhibitory postsynaptic potentials entrain nuclear cell spiking. With partial synchrony, nuclear neurons time-lock their spikes to the synchronous subpopulation of inputs, even when only 2 out of 40 afferents synchronize. In vivo, nuclear neurons reliably phase-lock to regular trains of molecular layer stimulation. Thus, cerebellar nuclear neurons can preferentially relay the spike timing of synchronized Purkinje cells to downstream premotor areas.

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Figure 1: Purkinje cell convergence and fast IPSCs in the cerebellar nuclei.
Figure 2: Entrainment of nuclear neuron spiking to synchronous IPSPs.
Figure 3: The synchronous subpopulation of Purkinje inputs sets spike timing of nuclear neurons.
Figure 4: Nuclear neurons phase-lock to molecular layer stimulation in vivo.

References

  1. 1

    Thach, W. T. Discharge of Purkinje and cerebellar nuclear neurons during rapidly alternating arm movements in the monkey. J. Neurophysiol. 31, 785–797 (1968)

    CAS  Article  Google Scholar 

  2. 2

    Chan-Palay, V. Cerebellar Dentate Nucleus: Organization, Cytology, and Transmitters (Springer, 1977)

    Book  Google Scholar 

  3. 3

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

    CAS  PubMed  Google Scholar 

  4. 4

    McDevitt, C. J., Ebner, T. J. & Bloedel, J. R. Relationships between simultaneously recorded Purkinje cells and nuclear neurons. Brain Res. 425, 1–13 (1987)

    CAS  Article  Google Scholar 

  5. 5

    Bell, C. C. & Grimm, R. J. Discharge properties of Purkinje cells recorded on single and double microelectrodes. J. Neurophysiol. 32, 1044–1055 (1969)

    CAS  Article  Google Scholar 

  6. 6

    Heck, D. H., Thach, W. T. & Keating, J. G. On-beam synchrony in the cerebellum as the mechanism for the timing and coordination of movement. Proc. Natl Acad. Sci. USA 104, 7658–7663 (2007)

    ADS  CAS  Article  Google Scholar 

  7. 7

    de Solages, C. et al. High-frequency organization and synchrony of activity in the Purkinje cell layer of the cerebellum. Neuron 58, 775–788 (2008)

    CAS  Article  Google Scholar 

  8. 8

    Wise, A. K., Cerminara, N. L., Marple-Horvat, D. E. & Apps, R. Mechanisms of synchronous activity in cerebellar Purkinje cells. J. Physiol. 588, 2373–2390 (2010)

    CAS  Article  Google Scholar 

  9. 9

    Welsh, J. P., Lang, E. J., Sugihara, I. & Llinas, R. Dynamic organization of motor control within the olivocerebellar system. Nature 374, 453–457 (1995)

    ADS  CAS  Article  Google Scholar 

  10. 10

    Ozden, I., Sullivan, M. R., Lee, H. M. & Wang, S. S. Reliable coding emerges from coactivation of climbing fibers in microbands of cerebellar Purkinje neurons. J. Neurosci. 29, 10463–10473 (2009)

    CAS  Article  Google Scholar 

  11. 11

    Schultz, S. R., Kitamura, K., Post-Uiterweer, A., Krupic, J. & Häusser, M. Spatial pattern coding of sensory information by climbing fiber-evoked calcium signals in networks of neighboring cerebellar Purkinje neurons. J. Neurosci. 29, 8005–8015 (2009)

    CAS  Article  Google Scholar 

  12. 12

    Gauck, V. & Jaeger, D. The control of rate and timing of spikes in the deep cerebellar nuclei by inhibition. J. Neurosci. 20, 3006–3016 (2000)

    CAS  Article  Google Scholar 

  13. 13

    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. 23, 8109–8118 (2003)

    CAS  Article  Google Scholar 

  14. 14

    Kistler, W. M. & De Zeeuw, C. I. Time windows and reverberating loops: a reverse-engineering approach to cerebellar function. Cerebellum 2, 44–54 (2003)

    Article  Google Scholar 

  15. 15

    Telgkamp, P. & Raman, I. M. Depression of inhibitory synaptic transmission between Purkinje cells and neurons of the cerebellar nuclei. J. Neurosci. 22, 8447–8457 (2002)

    CAS  Article  Google Scholar 

  16. 16

    Pedroarena, C. M. & Schwarz, C. Efficacy and short-term plasticity at GABAergic synapses between Purkinje and cerebellar nuclei neurons. J. Neurophysiol. 89, 704–715 (2003)

    CAS  Article  Google Scholar 

  17. 17

    Bengtsson, F., Ekerot, C.-F. & Jörntell, H. In vivo analysis of inhibitory synaptic inputs and rebounds in deep cerebellar nuclear neurons. PLoS ONE 6, e18822 (2011)

    ADS  CAS  Article  Google Scholar 

  18. 18

    Telgkamp, P., Padgett, D. E., Ledoux, V. A., Woolley, C. S. & Raman, I. M. Maintenance of high-frequency transmission at Purkinje to cerebellar nuclear synapses by spillover from boutons with multiple release sites. Neuron 41, 113–126 (2004)

    CAS  Article  Google Scholar 

  19. 19

    Pugh, J. R. & Raman, I. M. GABAA receptor kinetics in the cerebellar nuclei: evidence for detection of transmitter from distant release sites. Biophys. J. 88, 1740–1754 (2005)

    ADS  CAS  Article  Google Scholar 

  20. 20

    Bartos, M. et al. Fast synaptic inhibition promotes synchronized gamma oscillations in hippocampal interneuron networks. Proc. Natl Acad. Sci. USA 99, 13222–13227 (2002)

    ADS  CAS  Article  Google Scholar 

  21. 21

    Anchisi, D., Scelfo, B. & Tempia, F. Postsynaptic currents in deep cerebellar nuclei. J. Neurophysiol. 85, 323–331 (2001)

    CAS  Article  Google Scholar 

  22. 22

    Uusisaari, M. & Knopfel, T. GABAergic synaptic communication in the GABAergic and non-GABAergic cells in the deep cerebellar nuclei. Neuroscience 156, 537–549 (2008)

    CAS  Article  Google Scholar 

  23. 23

    Hoebeek, F. E., Witter, L., Ruigrok, T. J. & De Zeeuw, C. I. Differential olivo-cerebellar cortical control of rebound activity in the cerebellar nuclei. Proc. Natl Acad. Sci. USA 107, 8410–8415 (2010)

    ADS  CAS  Article  Google Scholar 

  24. 24

    Goossens, H. H. L. M. et al. Simple spike and complex spike activity of floccular Purkinje cells during the optokinetic reflex in mice lacking cerebellar long-term depression. Eur. J. Neurosci. 19, 687–697 (2004)

    CAS  Article  Google Scholar 

  25. 25

    Mauk, M. D. & Buonomano, D. V. The neural basis of temporal processing. Annu. Rev. Neurosci. 27, 307–340 (2004)

    CAS  Article  Google Scholar 

  26. 26

    Sugihara, I. et al. Projection of reconstructed single Purkinje cell axons in relation to the cortical and nuclear aldolase C compartments of the rat cerebellum. J. Comp. Neurol. 512, 282–304 (2009)

    CAS  Article  Google Scholar 

  27. 27

    Ruigrok, T. J. H., Pijpers, A., Goedknegt-Sabel, E. & Coulon, P. Multiple cerebellar zones are involved in the control of individual muscles: a retrograde transneuronal tracing study with rabies virus in the rat. Eur. J. Neurosci. 28, 181–200 (2008)

    Article  Google Scholar 

  28. 28

    Shinoda, Y., Futami, T., Mitoma, H. & Yokota, J. Morphology of single neurons in the cerebello-rubrospinal system. Behav. Brain Res. 28, 59–64 (1988)

    CAS  Article  Google Scholar 

  29. 29

    Toyama, K., Tsukahara, N., Kosaka, K. & Matsunami, K. Synaptic excitation of red nucleus neurones by fibres from interpositus nucleus. Exp. Brain Res. 11, 187–198 (1970)

    CAS  Article  Google Scholar 

  30. 30

    Tehovnik, E. J., Tolias, A. S., Sultan, F., Slocum, W. M. & Logothetis, N. K. Direct and indirect activation of cortical neurons by electrical microstimulation. J. Neurophysiol. 96, 512–521 (2006)

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We are grateful to J. R. Pugh for new analysis of data from ref. 19 on whole-cell GABA conductances. We thank D. Ferster, D. McLean and C. Woolley for comments on the manuscript. This work was supported by NIH grants R01-NS39395 (I.M.R.) and F32-NS067831 (A.L.P.).

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A.L.P. performed all experiments and analyses. A.L.P. and I.M.R. designed and interpreted experiments and wrote the manuscript.

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Correspondence to Abigail L. Person or Indira M. Raman.

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The authors declare no competing financial interests.

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Person, A., Raman, I. Purkinje neuron synchrony elicits time-locked spiking in the cerebellar nuclei. Nature 481, 502–505 (2012). https://doi.org/10.1038/nature10732

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