The tripartite synapse

  • Michael M. Halassa
  • Philip G. Haydon


Synaptic Transmission P2Y1 Receptor Excitatory Synaptic Transmission Schaffer Collateral Astrocytic Process 



Adenosine 5′-triphosphate




Supraoptic nucleus


  1. Anderson CM, Swanson RA (2000) Astrocyte glutamate transport: Review of properties, regulation, and physiological functions. Glia 32:1–14.PubMedCrossRefGoogle Scholar
  2. Adrian ED (1912) On the conduction of subnormal disturbances in normal nerve. J Physiol 45:389–412.PubMedGoogle Scholar
  3. Barbe MT, Monyer H, Bruzzone R (2006) Cell–Cell Communication Beyond Connexins: The Pannexin Channels. Physiology 21:103–114.PubMedCrossRefGoogle Scholar
  4. Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, Pilati E, Volterra A (2004) Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci 7:613–620.PubMedCrossRefGoogle Scholar
  5. Bowser DN, Khakh BS (2004) ATP excites interneurons and astrocytes to increase synaptic inhibition in neuronal networks. J Neurosci 24:8606–8620.PubMedCrossRefGoogle Scholar
  6. Butt AM, Kalsi A (2006) Inwardly rectifying potassium channels (Kir) in central nervous system glia: a special role for Kir4.1 in glial functions. J Cell Mol Med 10:33–44.PubMedCrossRefGoogle Scholar
  7. Cornell Bell AH, Finkbeiner SM, Cooper MS, Smith SJ (1990) Glutamate induces calcium waves in cultured astrocytes: long- range glial signaling. Science 247:470–473.PubMedCrossRefGoogle Scholar
  8. Ding S, Fellin T, Zhu Y, Lee SY, Auberson YP, Meaney DF, Coulter DA, Carmignoto G, Haydon PG (2007) Enhanced astrocytic Ca2+ signals contribute to neuronal excitotoxicity after status epilepticus. J Neurosci 27:10674–10684.PubMedCrossRefGoogle Scholar
  9. Fellin T, Pascual O, Gobbo S, Pozzan T, Haydon PG, Carmignoto G (2004) Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors. Neuron 43:729–743.PubMedCrossRefGoogle Scholar
  10. Fellin T, Pozzan T, Carmignoto G (2006) Purinergic receptors mediate two distinct glutamate release pathways in hippocampal astrocytes. J Biol Chem 281:4274–4284.PubMedCrossRefGoogle Scholar
  11. Guthrie PB, Knappenberger J, Segal M, Bennett MV, Charles AC, Kater SB (1999) ATP released from astrocytes mediates glial calcium waves. J Neurosci 19:520–528.PubMedGoogle Scholar
  12. Hertz L, Zielke HR (2004) Astrocytic control of glutamatergic activity: astrocytes as stars of the show. Trends Neurosci 27:735–743.PubMedCrossRefGoogle Scholar
  13. Jourdain P, Bergersen LH, Bhaukaurally K, Bezzi P, Santello M, Domercq M, Matute C, Tonello F, Gundersen V, Volterra A (2007) Glutamate exocytosis from astrocytes controls synaptic strength. Nat Neurosci 10:331–339.PubMedCrossRefGoogle Scholar
  14. Magistretti PJ (2006) Neuron-glia metabolic coupling and plasticity. J Exp Biol 209:2304–2311.PubMedCrossRefGoogle Scholar
  15. Montana V, Ni Y, Sunjara V, Hua X, Parpura V (2004) Vesicular glutamate transporter-dependent glutamate release from astrocytes. J Neurosci 24:2633–2642.PubMedCrossRefGoogle Scholar
  16. Mothet JP, Parent AT, Wolosker H, Brady RO, Jr., Linden DJ, Ferris CD, Rogawski MA, Snyder SH (2000) D-Serine is an endogenous ligand for the glycine site of the N-methyl-D-aspartate receptor. Proc Natl Acad Sci U S A 97:4926–4931.PubMedCrossRefGoogle Scholar
  17. Mothet JP, Pollegioni L, Ouanounou G, Martineau M, Fossier P, Baux G (2005) Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine. Proc Natl Acad Sci U S A 102:5606–5611.PubMedCrossRefGoogle Scholar
  18. Nedergaard M (1994) Direct signaling from astrocytes to neurons in cultures of mammalian brain cells. Science 263:1768–1771.PubMedCrossRefGoogle Scholar
  19. Panatier A, Theodosis DT, Mothet JP, Touquet B, Pollegioni L, Poulain DA, Oliet SH (2006) Glia-derived D-serine controls NMDA receptor activity and synaptic memory. Cell 125:775–784.PubMedCrossRefGoogle Scholar
  20. Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369:744–747.PubMedCrossRefGoogle Scholar
  21. Pascual O, Casper KB, Kubera C, Zhang J, Revilla-Sanchez R, Sul JY, Takano H, Moss SJ, McCarthy K, Haydon PG (2005) Astrocytic purinergic signaling coordinates synaptic networks. Science 310:113–116.PubMedCrossRefGoogle Scholar
  22. Pasti L, Volterra A, Pozzan T, Carmignoto G (1997) Intracellular calcium oscillations in astrocytes: a highly plastic, bidirectional form of communication between neurons and astrocytes in situ. J Neurosci 17:7817–7830.PubMedGoogle Scholar
  23. Scammell TE, Arrigoni E, Thompson MA, Ronan PJ, Saper CB, Greene RW (2003) Focal deletion of the adenosine A1 receptor in adult mice using an adeno-associated viral vector. J Neurosci 23:5762–5770.PubMedGoogle Scholar
  24. Schell MJ, Molliver ME, Snyder SH (1995) D-serine, an endogenous synaptic modulator: localization to astrocytes and glutamate-stimulated release. Proc Natl Acad Sci U S A 92:3948–3952.PubMedCrossRefGoogle Scholar
  25. Takano T, Kang J, Jaiswal JK, Simon SM, Lin JH, Yu Y, Li Y, Yang J, Dienel G, Zielke HR, Nedergaard M (2005) Receptor-mediated glutamate release from volume sensitive channels in astrocytes. Proc Natl Acad Sci U S A 102:16466–16471.PubMedCrossRefGoogle Scholar
  26. Tsacopoulos M, Magistretti PJ (1996) Metabolic coupling between glia and neurons. J Neurosci 16:877–885.PubMedGoogle Scholar
  27. Wang X, Lou N, Xu Q, Tian GF, Peng WG, Han X, Kang J, Takano T, Nedergaard M (2006) Astrocytic Ca(2+) signaling evoked by sensory stimulation in vivo. Nat Neurosci 9:816–823.PubMedCrossRefGoogle Scholar
  28. Wolosker H, Sheth KN, Takahashi M, Mothet JP, Brady RO, Jr., Ferris CD, Snyder SH (1999) Purification of serine racemase: biosynthesis of the neuromodulator D-serine. Proc Natl Acad Sci U S A 96:721–725.PubMedCrossRefGoogle Scholar
  29. Ye ZC, Wyeth MS, Baltan-Tekkok S, Ransom BR (2003) Functional hemichannels in astrocytes: a novel mechanism of glutamate release. J Neurosci 23:3588–3596.PubMedGoogle Scholar
  30. Zhang Q, Fukuda M, Van Bockstaele E, Pascual O, Haydon PG (2004a) Synaptotagmin IV regulates glial glutamate release. Proc Natl Acad Sci U S A 101:9441–9446.CrossRefGoogle Scholar
  31. Zhang Q, Pangrsic T, Kreft M, Krzan M, Li N, Sul JY, Halassa M, Van Bockstaele E, Zorec R, Haydon PG (2004b) Fusion-related release of glutamate from astrocytes. J Biol Chem 279:12724–12733.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Michael M. Halassa
    • 1
  • Philip G. Haydon
    • 1
  1. 1.University of Pennsylvania School of MedicineDepartment of NeuroscienceUSA

Personalised recommendations