Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Quantal events shape cerebellar interneuron firing

Abstract

Many small synaptic inputs or one large input are needed to influence principal cell firing, whereas individual quanta exert little influence. However, the role of a quantum may be greater for small interneurons with high input resistances. Using dynamic clamp recordings, we found that individual quanta strongly influence rat cerebellar stellate cell firing. When the frequency of synaptic inputs was low, the timing of recent spikes regulated the influence of excitatory quanta. In contrast, when input frequency was high, spike timing was less important than interactions with other inputs. Inhibitory quanta rapidly terminated firing, whereas small numbers of coincident excitatory quanta reliably and rapidly triggered firing. Our results suggest that stellate cells achieve temporal precision through coincidence detection and disynaptic inhibition, despite their high resistances and long membrane time constants. Thus, we propose that small interneurons can process synaptic inputs in a fundamentally different way from principal cells.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Single excitatory and inhibitory quanta influence stellate cell firing.
Figure 2: The influence of single excitatory quanta during spontaneous activity depends on spike timing.
Figure 3: Single quanta shape stellate cell firing during realistic synaptic activity.
Figure 4: The influence of single excitatory quanta during realistic synaptic activity depends on spike timing.
Figure 5: Inhibitory quanta shape the response to excitatory quanta.
Figure 6: Interactions between small numbers of excitatory quanta.
Figure 7: Small numbers of synchronous excitatory quanta trigger reliable and precise stellate cell firing.
Figure 8: Influence of inhibitory neuromodulation on the response to excitatory quanta.

Similar content being viewed by others

References

  1. Buzsaki, G. & Chrobak, J.J. Temporal structure in spatially organized neuronal ensembles: a role for interneuronal networks. Curr. Opin. Neurobiol. 5, 504–510 (1995).

    Article  CAS  Google Scholar 

  2. McBain, C.J. & Fisahn, A. Interneurons unbound. Nat. Rev. Neurosci. 2, 11–23 (2001).

    Article  CAS  Google Scholar 

  3. Abeles, M. Corticonics: Neural Circuits of the Cerebral Cortex (Cambridge Univ. Press, Cambridge, UK, 1991).

    Book  Google Scholar 

  4. Softky, W.R. & Koch, C. The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. J. Neurosci. 13, 334–350 (1993).

    Article  CAS  Google Scholar 

  5. Shadlen, M.N. & Newsome, W.T. Noise, neural codes and cortical organization. Curr. Opin. Neurobiol. 4, 569–579 (1994).

    Article  CAS  Google Scholar 

  6. Eccles, J.C. The Physiology of Nerve Cells (Johns Hopkins Press, Baltimore, Maryland, 1957).

    Google Scholar 

  7. Sayer, R.J., Redman, S.J. & Andersen, P. Amplitude fluctuations in small EPSPs recorded from CA1 pyramidal cells in the guinea pig hippocampal slice. J. Neurosci. 9, 840–850 (1989).

    Article  CAS  Google Scholar 

  8. Mason, A., Nicoll, A. & Stratford, K. Synaptic transmission between individual pyramidal neurons of the rat visual cortex in vitro. J. Neurosci. 11, 72–84 (1991).

    Article  CAS  Google Scholar 

  9. Eccles, J.C., Llinas, R. & Sasaki, K. The excitatory synaptic action of climbing fibers on the Pukinje cells of the cerebellum. J. Physiol. 182, 268–296 (1966).

    Article  CAS  Google Scholar 

  10. Cleland, B.G., Dubin, M.W. & Levick, W.R. Simultaneous recording of input and output of lateral geniculate neurones. Nat. New Biol. 231, 191–192 (1971).

    Article  CAS  Google Scholar 

  11. Zhang, S. & Trussell, L.O. A characterization of excitatory postsynaptic potentials in the avian nucleus magnocellularis. J. Neurophysiol. 72, 705–718 (1994).

    Article  CAS  Google Scholar 

  12. Fetz, E.E. & Gustafsson, B. Relation between shapes of post-synaptic potentials and changes in firing probability of cat motoneurones. J. Physiol. 341, 387–410 (1983).

    Article  CAS  Google Scholar 

  13. Barbour, B. Synaptic currents evoked in Purkinje cells by stimulating individual granule cells. Neuron 11, 759–769 (1993).

    Article  CAS  Google Scholar 

  14. Miles, R. Synaptic excitation of inhibitory cells by single CA3 hippocampal pyramidal cells of the guinea-pig in vitro. J. Physiol. 428, 61–77 (1990).

    Article  CAS  Google Scholar 

  15. Bennett, B.D. & Wilson, C.J. Synaptic regulation of action potential timing in neostriatal cholinergic interneurons. J. Neurosci. 18, 8539–8549 (1998).

    Article  CAS  Google Scholar 

  16. Fricker, D. & Miles, R. EPSP amplification and the precision of spike timing in hippocampal neurons. Neuron 28, 559–569 (2000).

    Article  CAS  Google Scholar 

  17. Galarreta, M. & Hestrin, S. Spike transmission and synchrony detection in networks of GABAergic interneurons. Science 292, 2295–2299 (2001).

    Article  CAS  Google Scholar 

  18. Oertel, D. The role of intrinsic neuronal properties in the encoding of auditory information in the cochlear nuclei. Curr. Opin. Neurobiol. 1, 221–228 (1991).

    Article  CAS  Google Scholar 

  19. Miles, R. & Wong, R.K.S. Excitatory synaptic interactions between CA3 neurones in the guinea-pig hippocampus. J. Physiol. 373, 397–418 (1986).

    Article  CAS  Google Scholar 

  20. Pouille, F. & Scanziani, M. Enforcement of temporal fidelity in pyramidal cells by somatic feed-forward inhibition. Science 293, 1159–1163 (2001).

    Article  CAS  Google Scholar 

  21. Geiger, J.R., Lubke, J., Roth, A., Frotscher, M. & Jonas, P. Submillisecond AMPA receptor-mediated signaling at a principal neuron-interneuron synapse. Neuron 18, 1009–1023 (1997).

    Article  CAS  Google Scholar 

  22. Mann-Metzer, P. & Yarom, Y. Jittery trains induced by synaptic-like currents in cerebellar inhibitory interneurons. J. Neurophysiol. 87, 149–156 (2002).

    Article  Google Scholar 

  23. Midtgaard, J. Membrane properties and synaptic responses of Golgi cells and stellate cells in the turtle cerebellum in vitro. J. Physiol. 457, 329–354 (1992).

    Article  CAS  Google Scholar 

  24. Bennett, B.D., Callaway, J.C. & Wilson, C.J. Intrinsic membrane properties underlying spontaneous tonic firing in neostriatal cholinergic interneurons. J. Neurosci. 20, 8493–8503 (2000).

    Article  CAS  Google Scholar 

  25. Reyes, A.D. & Fetz, E.E. Two modes of interspike interval shortening by brief transient depolarizations in cat neocortical neurons. J. Neurophysiol. 69, 1661–1672 (1993).

    Article  CAS  Google Scholar 

  26. Abeles, M. Role of the cortical neuron: integrator or coincidence detector? Isr. J. Med. Sci. 18, 83–92 (1982).

    CAS  PubMed  Google Scholar 

  27. Mainen, Z.F. & Sejnowski, T.J. Reliability of spike timing in neocortical neurons. Science 268, 1503–1506 (1995).

    Article  CAS  Google Scholar 

  28. Stevens, C.F. & Zador, A.M. Input synchrony and the irregular firing of cortical neurons. Nat. Neurosci. 1, 210–217 (1998).

    Article  CAS  Google Scholar 

  29. Palay, S.L. & Chan-Palay, V. Cerebellar Cortex p. 348 (Springer-Verlag, New York, 1974).

    Book  Google Scholar 

  30. Llano, I. & Gerschenfeld, H.M. Inhibitory synaptic currents in the stellate cells of rat cerebellar slices. J. Physiol. 468, 177–200 (1993).

    Article  CAS  Google Scholar 

  31. Callaway, J.C., Lasser-Ross, N. & Ross, W.N. IPSPs strongly inhibit climbing fiber-activated [Ca2+]i increases in the dendrites of cerebellar Purkinje neurons. J. Neurosci. 15, 2777–2787 (1995).

    Article  CAS  Google Scholar 

  32. Midtgaard, J. Stellate cell inhibition of Purkinje cells in the turtle cerebellum in vitro. J. Physiol. 457, 355–367 (1992).

    Article  CAS  Google Scholar 

  33. Hausser, M. & Clark, B.A. Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron 19, 665–678 (1997).

    Article  CAS  Google Scholar 

  34. Jaeger, D. & Bower, J.M. Synaptic control of spiking in cerebellar Purkinje cells: dynamic current clamp based on model conductances. J. Neurosci. 19, 6090–6101 (1999).

    Article  CAS  Google Scholar 

  35. Robinson, H.P. & Kawai, N. Injection of digitally synthesized synaptic conductance transients to measure the integrative properties of neurons. J. Neurosci. Methods 49, 157–165 (1993).

    Article  CAS  Google Scholar 

  36. Sharp, A.A., O'Neil, M.B., Abbott, L.F. & Marder, E. Dynamic clamp: computer-generated conductances in real neurons. J. Neurophysiol. 69, 992–995 (1993).

    Article  CAS  Google Scholar 

  37. Kreitzer, A.C., Carter, A.G. & Regehr, W.G. Inhibition of interneuron firing extends the spread of endocannabinoid signaling in the cerebellum. Neuron 34, 787–796 (2002).

    Article  CAS  Google Scholar 

  38. Eccles, J.C., Llinas, R. & Sasaki, K. The inhibitory interneurones within the cerebellar cortex. Exp. Brain Res. 1, 1–16 (1966).

    Article  CAS  Google Scholar 

  39. Carter, A.G. & Regehr, W.G. Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse. J. Neurosci. 20, 4423–4434 (2000).

    Article  CAS  Google Scholar 

  40. Nusser, Z., Naylor, D. & Mody, I. Synapse-specific contribution of the variation of transmitter concentration to the decay of inhibitory postsynaptic currents. Biophys. J. 80, 1251–1261 (2001).

    Article  CAS  Google Scholar 

  41. Armstrong, D.M. & Rawson, J.A. Activity patterns of cerebellar cortical neurones and climbing fibre afferents in the awake cat. J. Physiol. 289, 425–448 (1979).

    Article  CAS  Google Scholar 

  42. Sui, J.L., Chan, K., Langan, M.N., Vivaudou, M. & Logothetis, D.E. G protein gated potassium channels. Adv. Second Messenger Phosphoprotein Res. 33, 179–201 (1999).

    Article  CAS  Google Scholar 

  43. Mark, M.D. & Herlitze, S. G-protein mediated gating of inward-rectifier K+ channels. Eur. J. Biochem. 267, 5830–5836 (2000).

    Article  CAS  Google Scholar 

  44. Otmakhov, N., Shirke, A.M. & Malinow, R. Measuring the impact of probabilistic transmission on neuronal output. Neuron 10, 1101–1111 (1993).

    Article  CAS  Google Scholar 

  45. Kondo, S. & Marty, A. Synaptic currents at individual connections among stellate cells in rat cerebellar slices. J. Physiol. 509, 221–232 (1998).

    Article  CAS  Google Scholar 

  46. Gulyas, A.I., Miles, R., Hajos, N. & Freund, T.F. Precision and variability in postsynaptic target selection of inhibitory cells in the hippocampal CA3 region. Eur. J. Neurosci. 5, 1729–1751 (1993).

    Article  CAS  Google Scholar 

  47. Miles, R., Toth, K., Gulyas, A.I., Hajos, N. & Freund, T.F. Differences between somatic and dendritic inhibition in the hippocampus. Neuron 16, 815–823 (1996).

    Article  CAS  Google Scholar 

  48. Koch, C. Biophysics of Computation (Oxford Univ. Press, New York, 1999).

    Google Scholar 

  49. Ito, M. The Cerebellum and Neural Control p. 580 (Raven Press, New York, 1984).

    Google Scholar 

  50. Auger, C. & Marty, A. Heterogeneity of functional synaptic parameters among single release sites. Neuron 19, 139–150 (1997).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Beierlein, D. Blitz, S. Brenowitz, S. Brown, K. Foster, A. Kreitzer, P. Safo, B. Sabatini, M. Xu-Friedman and G. Yellen for comments on the manuscript. This work was supported by the National Institutes of Health (NIH R01-NS32405-01).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Wade G. Regehr.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carter, A., Regehr, W. Quantal events shape cerebellar interneuron firing. Nat Neurosci 5, 1309–1318 (2002). https://doi.org/10.1038/nn970

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn970

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing