Molecular Mechanism of Long-Term Plasticity at Cerebellar Inhibitory Synapses

Chapter

Abstract

The efficacy of synaptic transmission changes depending on the neuronal activity in the central nervous system. Such synaptic plasticity underlies experience-dependent refinement of information processing in a neuronal network, and is regarded as a cellular basis for learning and memory. Compared with excitatory synapses, little has been clarified about the regulatory mechanism of plasticity at inhibitory synapses. In this chapter, we summarize recent advances in understanding the molecular mechanism of inhibitory synaptic plasticity in the cerebellum. The GABAergic synapses on a Purkinje neuron undergo long-term potentiation of postsynaptic GABAA receptor (GABAAR) responsiveness in response to the postsynaptic depolarization, which is called rebound potentiation (RP). The mechanism of RP regulation has been studied at the molecular level using electrophysiological experiments combined with molecular biological techniques, fluorescent imaging and systems biological computer simulation. We here describe how the induction of RP is regulated through complicated interaction of intracellular signaling cascades including protein kinases/phosphatases, and how a GABAAR binding protein is implicated in the establishment and maintenance of inhibitory synaptic plasticity.

References

  1. Aizenman CD, Manis PB, Linden DJ (1998) Polarity of long-term synaptic gain change is related to postsynaptic spike firing at a cerebellar inhibitory synapse. Neuron 21:827–835CrossRefPubMedGoogle Scholar
  2. Bailey CH, Giustetto M, Huang YY et al. (2000) Is heterosynaptic modulation essential for stabilizing Hebbian plasticity and memory? Nat Rev Neurosci 1:11–20CrossRefPubMedGoogle Scholar
  3. Bhalla US, Iyengar R (1999) Emergent properties of networks of biological signaling pathways. Science 283:381–387CrossRefPubMedGoogle Scholar
  4. Brandman O, Meyer T (2008) Feedback loops shape cellular signals in space and time. Science 322:390–395CrossRefPubMedGoogle Scholar
  5. Brandon N, Jovanovic J, Moss S (2002) Multiple roles of protein kinases in the modulation of γ-aminobutyric acidA receptor function and cell surface expression. Pharmacol Ther 94:113–122CrossRefPubMedGoogle Scholar
  6. Chen Z, Olsen RW (2007) GABAA receptor associated proteins: a key factor regulating GABAA receptor function. J Neurochem 100:279–294CrossRefPubMedGoogle Scholar
  7. Duguid IC, Smart TG (2004) Retrograde activation of presynaptic NMDA receptors enhances GABA release at cerebellar interneuron-Purkinje cell synapses. Nat Neurosci 7:525–533CrossRefPubMedGoogle Scholar
  8. Everitt AB, Luu T, Cromer B et al. (2004) Conductance of recombinant GABAA channels is increased in cells co-expressing GABAA receptor-associated protein. J Biol Chem 279:21701–21706CrossRefPubMedGoogle Scholar
  9. Gaiarsa JL, Caillard O, Ben-Ari Y (2002) Long-term plasticity at GABAergic and glycinergic synapses: mechanisms and functional significance. Trends Neurosci 25:564–570CrossRefPubMedGoogle Scholar
  10. Giese KP, Fedorov NB, Filipkowski RK et al. (1998) Autophosphorylation at Thr286 of the alpha calcium-calmodulin kinase II in LTP and learning. Science 279:870–873CrossRefPubMedGoogle Scholar
  11. 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 4:467–475PubMedGoogle Scholar
  12. Hashimoto Y, Sharma RK, Soderling TR (1989) Regulation of Ca2+/calmodulin-dependent cyclic nucleotide phosphodiesterase by the autophosphorylated form of Ca2+/calmodulin-dependent protein kinase II. J Biol Chem 264:10884–10887PubMedGoogle Scholar
  13. Hemmings HC Jr, Greengard P, Tung HY et al. (1984) DARPP-32, a dopamine-regulated neuronal phosphoprotein, is a potent inhibitor of protein phosphatase-1. Nature 310:503–505CrossRefPubMedGoogle Scholar
  14. Houston CM, Hosie AM, Smart TG (2008) Distinct regulation of β2 and β3 subunit-containing cerebellar synaptic GABAA receptors by calcium/calmodulin-dependent protein kinase II. J Neurosci 28:7574–7584CrossRefPubMedGoogle Scholar
  15. Houston CM, Smart TG (2006) CaMK-II modulation of GABAA receptors expressed in HEK293, NG108-15 and rat cerebellar granule neurons. Eur J Neurosci 24:2504–2514CrossRefPubMedGoogle Scholar
  16. Ito M (2001) Cerebellar long-term depression: characterization, signal transduction, and functional roles. Physiol Rev 81:1143–1195PubMedGoogle Scholar
  17. Kandel ER (2001) The molecular biology of memory storage: a dialogue between genes and synapses. Science 294:1030–1038CrossRefPubMedGoogle Scholar
  18. Kanematsu T, Mizokami A, Watanabe K et al. (2007) Regulation of GABAA-receptor surface expression with special reference to the involvement of GABARAP (GABAA receptor-associated protein) and PRIP (phospholipase C-related, but catalytically inactive protein). J Pharmacol Sci 104:285–292CrossRefPubMedGoogle Scholar
  19. Kano M (1995) Plasticity of inhibitory synapses in the brain: a possible memory mechanism that has been overlooked. Neurosci Res 21:177–182.CrossRefPubMedGoogle Scholar
  20. Kano M, Rexhausen U, Dreessen J et al. (1992) Synaptic excitation produces a long-lasting rebound potentiation of inhibitory synaptic signals in cerebellar Purkinje cells. Nature 356:601–604CrossRefPubMedGoogle Scholar
  21. Kano M, Kano M, Fukunaga K et al. (1996) Ca2+-induced rebound potentiation of γ-aminobutyric acid-mediated currents requires activation of Ca2+/calmodulin-dependent kinase II. Proc Natl Acad Sci USA 93:13351–13356CrossRefPubMedGoogle Scholar
  22. Kawaguchi S, Hirano T (2000) Suppression of inhibitory synaptic potentiation by presynaptic activity through postsynaptic GABAB receptors in a Purkinje neuron. Neuron 27:339–347CrossRefPubMedGoogle Scholar
  23. Kawaguchi S, Hirano T (2002) Signaling cascade regulating long-term potentiation of GABAA receptor responsiveness in cerebellar Purkinje neurons. J Neurosci 22:3969–3976PubMedGoogle Scholar
  24. Kawaguchi S, Hirano T (2006) Integrin α3β1 suppresses long-term potentiation at inhibitory synapses on the cerebellar Purkinje neuron. Mol Cell Neurosci 31:416–426CrossRefPubMedGoogle Scholar
  25. Kawaguchi S, Hirano T (2007) Sustained structural change of GABAA receptor-associated protein underlies long-term potentiation at inhibitory synapses on a cerebellar Purkinje neuron. J Neurosci 27:6788–6799CrossRefPubMedGoogle Scholar
  26. Kitagawa Y, Hirano T, Kawaguchi S (2009) Prediction and validation of a mechanism to control the threshold for inhibitory synaptic plasticity. Mol Syst Biol 5:280CrossRefPubMedGoogle Scholar
  27. Kittler JT, Rostaing P, Schiavo G et al. (2001) The subcellular distribution of GABARAP and its ability to interact with NSF suggest a role for this protein in the intracellular transport of GABAA receptors. Mol Cell Neurosci 18:13–25CrossRefPubMedGoogle Scholar
  28. Kneussel M (2002) Dynamic regulation of GABAA receptors at synaptic sites. Brain Res Brain Res Rev 39:74–83CrossRefPubMedGoogle Scholar
  29. Kneussel M, Haverkamp S, Fuhrmann JC et al. (2000) The γ-aminobutyric acid type A receptor (GABAAR)- associated protein GABARAP interacts with gephyrin but is not involved in receptor anchoring at the synapse. Proc Natl Acad Sci USA 97:8594–8599CrossRefPubMedGoogle Scholar
  30. Komatsu Y (1994) Age-dependent long-term potentiation of inhibitory synaptic transmission in rat visual cortex. J Neurosci 14:6488–6499PubMedGoogle Scholar
  31. Komatsu Y (1996) GABAB receptors, monoamine receptors, and postsynaptic inositol trisphosphate-induced Ca2+ release are involved in the induction of long-term potentiation at visual cortical inhibitory synapses. J Neurosci 16:6342–6352PubMedGoogle Scholar
  32. Leil TA, Chen ZW, Chang CS et al. (2004) GABAA receptor- associated protein traffics GABAA receptors to the plasma membrane in neurons. J Neurosci 24:11429–11438CrossRefPubMedGoogle Scholar
  33. Lisman JE, Zhabotinsky AM (2001) A model of synaptic memory: a CaMKII/PP1 switch that potentiates transmission by organizing an AMPA receptor anchoring assembly. Neuron 31:191–201CrossRefPubMedGoogle Scholar
  34. Llano I, Leresche N, Marty A (1991) Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents. Neuron 6:565–574CrossRefPubMedGoogle Scholar
  35. Luscher B, Keller CA (2004) Regulation of GABAA receptor trafficking, channel activity, and functional plasticity of inhibitory synapses. Pharm Therap 102:195–221CrossRefGoogle Scholar
  36. Luu T, Gage PW, Tierney ML (2006) GABA increases both the conductance and mean open time of recombinant GABAA channels co-expressed with GABARAP. J Biol Chem 281:35699–35708CrossRefPubMedGoogle Scholar
  37. Malenka RC, Nocoll RA (1999) Long-term potentiation-a decade of progress? Science 285:1870–1874CrossRefPubMedGoogle Scholar
  38. Marsden KC, Beattie JB, Friedenthal J et al. (2007) NMDA receptor activation potentiates inhibitory transmission through GABA receptor-associated protein-dependent exocytosis of GABAA receptors. J Neurosci 27:14326–14337CrossRefPubMedGoogle Scholar
  39. Marty A, Llano I (1995) Modulation of inhibitory synapses in the mammalian brain. Curr Opin Neurobiol 5:335–341CrossRefPubMedGoogle Scholar
  40. Miller SG, Kennedy MB (1986) Regulation of brain type II Ca2+/calmodulin- dependent protein kinase by autophosphorylation: a Ca2+-triggered molecular switch. Cell 44:861–870CrossRefPubMedGoogle Scholar
  41. Mittmann W, Hausser M (2007) Linking synaptic plasticity and spike output at excitatory and inhibitory synapses onto cerebellar Purkinje cells. J Neurosci 27:5559–5570CrossRefPubMedGoogle Scholar
  42. Moss SJ, Smart TG (1996) Modulation of amino acid-gated ion channels by protein phosphorylation. Int Rev Neurobiol 39:1–52CrossRefPubMedGoogle Scholar
  43. Moss SJ, Smart TG (2001) Constructing inhibitory synapses. Nat Rev Neurosci 2:240–250CrossRefPubMedGoogle Scholar
  44. Nusser Z, Hajos N, Somogyi P et al. (1998) Increased number of synaptic GABAA receptors underlies potentiation at hippocampal inhibitory synapses. Nature 395:172–177CrossRefPubMedGoogle Scholar
  45. Nymann-Andersen J, Wang H, Chen L et al. (2002) Subunit specificity and interaction domain between GABAA receptor-associated protein (GABARAP) and GABAA receptors. J Neurochem 80:815–823CrossRefPubMedGoogle Scholar
  46. Sugiyama Y, Kawaguchi S, Hirano T (2008) mGluR1-mediated facilitation of long-term potentiation at inhibitory synapses on a cerebellar Purkinje neuron. Eur J Neurosci 27:884–896CrossRefPubMedGoogle Scholar
  47. Wang H, Bedford FK, Brandon NJ et al. (1999) GABAA-receptor-associated protein links GABAA receptors and the cytoskeleton. Nature 397:69–72CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Biophysics, Graduate School of ScienceKyoto UniversityKyotoJapan

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