Skip to main content
Log in

Long-Term Synaptic Plasticity in Cerebellar Stellate Cells

  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Inhibitory transmission controls the action potential firing rate and pattern of Purkinje cell activity in the cerebellum. A long-term change in inhibitory transmission is likely to have a profound effect on the activity of cerebellar neuronal circuits. However, little is known about how neuronal activity regulates synaptic transmission in GABAergic inhibitory interneurons (stellate/basket cells) in the cerebellar cortex. We have examined how glutamate released from parallel fibers (the axons of granule cells) influences postsynaptic alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors in stellate cells and modulates γ-aminobutyric acid (GABA) release from these neurons. First, we found that burst stimulation of presynaptic parallel fibers changes the subunit composition of post-synaptic AMPA receptors from GluR2-lacking to GluR2-containing receptors. This switch reduces the Ca2+ permeability of AMPA receptors and the excitatory postsynaptic potential amplitude and prolongs the duration of the synaptic current, producing a qualitative change in synaptic transmission. This switch in AMPA receptor phenotype can be induced by activation of extrasynaptic N-methyl-d-aspartate (NMDA) receptors and involves PICK1 and the activation of protein kinase C. Second, activation of presynaptic NMDA receptors triggers a lasting increase in GABA release from stellate cells. These changes may provide a cellular mechanism underlying associative learning involving the cerebellum.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.

Similar content being viewed by others

References

  1. Raymond JL, Lisberger SG, Mauk MD (1996) The cerebellum: a neuronal learning machine? Science 272(5265):1126–1131

    Article  PubMed  CAS  Google Scholar 

  2. Ito M (1989) Long-term depression. Annu Rev Neurosci 12:85–102

    Article  PubMed  CAS  Google Scholar 

  3. Thompson RF (1990) Neural mechanisms of classical conditioning in mammals. Philos Trans R Soc Lond B Biol Sci 329(1253):161–170

    Article  PubMed  CAS  Google Scholar 

  4. Medina JF, Mauk MD (2000) Computer simulation of cerebellar information processing. Nat Neurosci 3(Suppl):1205–1211

    Article  PubMed  CAS  Google Scholar 

  5. Hansel C, Linden DJ (2000) Long-term depression of the cerebellar climbing fiber–Purkinje neuron synapse. Neuron 26(2):473–482

    Article  PubMed  CAS  Google Scholar 

  6. Hansel C, Linden DJ, D’Angelo E (2001) Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum. Nat Neurosci 4(5):467–475

    PubMed  CAS  Google Scholar 

  7. Hausser M, Clark BA (1997) Tonic synaptic inhibition modulates neuronal output pattern and spatiotemporal synaptic integration. Neuron 19(3):665–678

    Article  PubMed  CAS  Google Scholar 

  8. Jaeger D, Bower JM (1999) Synaptic control of spiking in cerebellar Purkinje cells: dynamic current clamp based on model conductances. J Neurosci 19(14):6090–6101

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  10. Rancillac A, Crepel F (2004) Synapses between parallel fibres and stellate cells express long-term changes in synaptic efficacy in rat cerebellum. J Physiol 554(Pt 3):707–720

    PubMed  CAS  Google Scholar 

  11. Liu SQ, Cull-Candy SG (2000) Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype. Nature 405(6785):454–458

    Article  PubMed  CAS  Google Scholar 

  12. Clark BA, Cull-Candy SG (2002) Activity-dependent recruitment of extrasynaptic NMDA receptor activation at an AMPA receptor-only synapse. J Neurosci 22(11):4428–4436

    PubMed  CAS  Google Scholar 

  13. Liu SJ, Cull-Candy SG (2002) Activity-dependent change in AMPA receptor properties in cerebellar stellate cells. J Neurosci 22(10):3881–3889

    PubMed  CAS  Google Scholar 

  14. Liu SJ, Cull-Candy SG (2005) Subunit interaction with PICK and GRIP controls Ca2+ permeability of AMPARs at cerebellar synapses. Nat Neurosci 8(6):768–775

    Article  PubMed  CAS  Google Scholar 

  15. Liu SJ, Zukin RS (2007) Ca2+-permeable AMPA receptors in synaptic plasticity and neuronal death. Trends Neurosci 30(3):126–134

    Article  PubMed  CAS  Google Scholar 

  16. Chadderton P, Margrie TW, Hausser M (2004) Integration of quanta in cerebellar granule cells during sensory processing. Nature 428(6985):856–860

    Article  PubMed  CAS  Google Scholar 

  17. Carter AG, Regehr WG (2000) Prolonged synaptic currents and glutamate spillover at the parallel fiber to stellate cell synapse. J Neurosci 20(12):4423–4434

    PubMed  CAS  Google Scholar 

  18. Bowie D, Mayer ML (1995) Inward rectification of both AMPA and kainate subtype glutamate receptors generated by polyamine-mediated ion channel block. Neuron 15(2):453–462

    Article  PubMed  CAS  Google Scholar 

  19. Kamboj SK, Swanson GT, Cull-Candy SG (1995) Intracellular spermine confers rectification on rat calcium-permeable AMPA and kainate receptors. J Physiol 486(Pt 2):297–303

    PubMed  CAS  Google Scholar 

  20. Koh DS, Burnashev N, Jonas P (1995) Block of native Ca(2+)-permeable AMPA receptors in rat brain by intracellular polyamines generates double rectification. J Physiol 486(Pt 2):305–312

    PubMed  CAS  Google Scholar 

  21. Washburn MS, Numberger M, Zhang S, Dingledine R (1997) Differential dependence on GluR2 expression of three characteristic features of AMPA receptors. J Neurosci 17(24):9393–9406

    PubMed  CAS  Google Scholar 

  22. Sun L, Liu SJ (2007) Activation of extrasynaptic NMDA receptors induces a PKC-dependent switch in AMPA receptor subtypes in mouse cerebellar stellate cells. J Physiol 583(2):537–553

    Article  PubMed  CAS  Google Scholar 

  23. Perez JL, Khatri L, Chang C, Srivastava S, Osten P, Ziff EB (2001) PICK1 targets activated protein kinase Calpha to AMPA receptor clusters in spines of hippocampal neurons and reduces surface levels of the AMPA-type glutamate receptor subunit 2. J Neurosci 21(15):5417–5428

    PubMed  CAS  Google Scholar 

  24. Gardner SM, Takamiya K, Xia J, Suh JG, Johnson R, Yu S et al (2005) Calcium-permeable AMPA receptor plasticity is mediated by subunit-specific interactions with PICK1 and NSF. Neuron 45(6):903–915

    Article  PubMed  CAS  Google Scholar 

  25. Leitges M, Kovac J, Plomann M, Linden DJ (2004) A unique PDZ ligand in PKCalpha confers induction of cerebellar long-term synaptic depression. Neuron 44(4):585–594

    Article  PubMed  CAS  Google Scholar 

  26. Dev KK, Nishimune A, Henley JM, Nakanishi S (1999) The protein kinase C alpha binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits. Neuropharmacology 38(5):635–644

    Article  PubMed  CAS  Google Scholar 

  27. Xia J, Chung HJ, Wihler C, Huganir RL, Linden DJ (2000) Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron 28(2):499–510

    Article  PubMed  CAS  Google Scholar 

  28. Steinberg JP, Takamiya K, Shen Y, Xia J, Rubio ME, Yu S et al (2006) Targeted in vivo mutations of the AMPA receptor subunit GluR2 and its interacting protein PICK1 eliminate cerebellar long-term depression. Neuron 49(6):845–860

    Article  PubMed  CAS  Google Scholar 

  29. Kano M, Rexhausen U, Dreessen J, Konnerth A (1992) Synaptic excitation produces a long-lasting rebound potentiation of inhibitory synaptic signals in cerebellar Purkinje cells. Nature 356(6370):601–604

    Article  PubMed  CAS  Google Scholar 

  30. Kano M, Fukunaga K, Konnerth A (1996) Ca(2+)-induced rebound potentiation of gamma-aminobutyric acid-mediated currents requires activation of Ca2+/calmodulin-dependent kinase II. Proc Natl Acad Sci USA 93(23):13351–13356

    Article  PubMed  CAS  Google Scholar 

  31. Kawaguchi S, Hirano T (2000) Suppression of inhibitory synaptic potentiation by presynaptic activity through postsynaptic GABA(B) receptors in a Purkinje neuron. Neuron 27(2):339–347

    Article  PubMed  CAS  Google Scholar 

  32. Kawaguchi SY, Hirano T (2002) Signaling cascade regulating long-term potentiation of GABA(A) receptor responsiveness in cerebellar Purkinje neurons. J Neurosci 22(10):3969–3976

    PubMed  CAS  Google Scholar 

  33. Liu SJ, Lachamp P (2006) The activation of excitatory glutamate receptors evokes a long-lasting increase in the release of GABA from cerebellar stellate cells. J Neurosci 26(36):9332–9339

    Article  PubMed  CAS  Google Scholar 

  34. Pouzat C, Hestrin S (1997) Developmental regulation of basket/stellate cell–>Purkinje cell synapses in the cerebellum. J Neurosci 17(23):9104–9112

    PubMed  CAS  Google Scholar 

  35. Liu SJ (2007) Biphasic modulation of GABA release from stellate cells by glutamatergic receptor subtypes. J Neurophysiol 98(1):550–556

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by National Science Foundation Grant IBN-0344559 and National Institutes of Health Grant NS58867.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Siqiong June Liu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liu, S.J., Lachamp, P., Liu, Y. et al. Long-Term Synaptic Plasticity in Cerebellar Stellate Cells. Cerebellum 7, 559–562 (2008). https://doi.org/10.1007/s12311-008-0057-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-008-0057-5

Keywords

Navigation