Neurons and glia are the principal cellular components of the nervous system. Although the glia are 10 times more numerous than neurons, until recently they were thought to be passive cells that monitor and support the active neurons by taking up used neurotransmitters from the synapses. In the past few years, this concept has been challenged by the findings that Ca2+ waves spread from one astrocyte to another via Ca2+-and SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor)-dependent gliotransmitter release in pure cultures of astrocytes, raising the possibility that glia are not so passive as previously thought. This hypothesis was further advanced by two recent reports, which demonstrated that astrocytes release glutamate via vesicular exocytosis in response to stimuli. The kinetics of single vesicle exocytosis is distinct from its neural equivalent, because in response to physiological stimulation, gliotransmitter release is exclusively in the mode of “kiss and run.” These advances were made possible by newly available techniques for single vesicle recordings, which will also be briefly reviewed here.
Araque A, Li N, Doyle RT, Haydon PG. 2000. SNARE protein-dependent glutamate release from astrocytes. J Neurosci20:666–673.
2.
Aravanis AM, Pyle JL, Tsien RW. 2003. Single synaptic vesicles fusing transiently and successively without loss of identity. Nature423:643–647.
3.
Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, Pilati E, and others. 2004. Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci7:613–620.
4.
Bezzi P, Volterra A. 2001. A neuron-glia signalling network in the active brain. Curr Opin Neurobiol11:387–394.
5.
Bruns D, Jahn R. 1995. Real-time measurement of transmitter release from single synaptic vesicles. Nature377:62–65.
6.
Carmignoto G. 2000. Reciprocal communication systems between astrocytes and neurones. Prog Neurobiol62:561–581.
7.
Chen X, Wang L, Zhou Y, Zheng LH, Zhou Z. 2005. “Kiss-and-run” glutamate secretion in cultured and freshly isolated rat hippocampal astrocytes. J Neurosci25:9236–9243.
8.
Chow RH, von Ruden L, Neher E. 1992. Delay in vesicle fusion revealed by electrochemical monitoring of single secretory events in adrenal chromaffin cells. Nature356:60–63.
9.
Gandhi SP, Stevens CF. 2003. Three modes of synaptic vesicular recycling revealed by single-vesicle imaging. Nature423:607–613.
10.
Haydon PG. 2001. GLIA: listening and talking to the synapse. Nat Rev Neurosci2:185–193.
11.
Hume RI, Role LW, Fischbach GD. 1983. Acetylcholine release from growth cones detected with patches of acetylcholine receptor-rich membranes. Nature305:632–634.
12.
Jahn R, Sudhof TC. 1999. Membrane fusion and exocytosis. Annu Rev Biochem68:863–911.
13.
Kim KT, Koh DS, Hille B. 2000. Loading of oxidizable transmitters into secretory vesicles permits carbon-fiber amperometry. J Neurosci20:RC101–RC101.
14.
Montana V, Ni Y, Sunjara V, Hua X, Parpura V. 2004. Vesicular glutamate transporter-dependent glutamate release from astrocytes. J Neurosci24:2633–2642.
15.
Nedergaard M, Takano T, Hansen AJ. 2002. Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci3:748–755.
16.
Parri HR, Gould TM, Crunelli V. 2001. Spontaneous astrocytic Ca2+ oscillations in situ drive NMDAR-mediated neuronal excitation. Nat Neurosci4:803–812.
17.
Pascual O, Casper KB, Kubera C, Zhang J, Revilla-Sanchez R, Sul JY, and others. 2005. Astrocytic purinergic signaling coordinates synaptic networks. Science310:113–116.
18.
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 Neurosci17:7817–7830.
19.
Pasti L, Zonta M, Pozzan T, Vicini S, Carmignoto G. 2001. Cytosolic calcium oscillations in astrocytes may regulate exocytotic release of glutamate. J Neurosci21:477–484.
20.
Rettig J, Neher E. 2002. Emerging roles of presynaptic proteins in Ca++-triggered exocytosis. Science298:781–785.
21.
Staal RG, Mosharov EV, Sulzer D. 2004. Dopamine neurons release transmitter via a flickering fusion pore. Nat Neurosci7:341–346.
22.
Steyer JA, Almers W. 2001. A real-time view of life within 100 nm of the plasma membrane. Nat Rev Mol Cell Biol2:268–275.
23.
Urena J, Fernandez-Chacon R, Benot AR, Alvarez de Toledo GA, Lopez-Barneo J. 1994. Hypoxia induces voltage-dependent Ca2+ entry and quantal dopamine secretion in carotid body glomus cells. Proc Natl Acad Sci U S A91:10208–10211.
24.
Weber T, Zemelman BV, McNew JA, Westermann B, Gmachl M, Parlati F, and others. 1998. SNAREpins: minimal machinery for membrane fusion. Cell92:759–772.
25.
Wightman RM, Jankowski JA, Kennedy RT, Kawagoe KT, Schroeder TJ, Leszczyszyn DJ, and others. 1991. Temporally resolved catecholamine spikes correspond to single vesicle release from individual chromaffin cells. Proc Natl Acad Sci U S A88:10754–10758.
26.
Young SH, Poo MM. 1983. Spontaneous release of transmitter from growth cones of embryonic neurones. Nature305:634–637.
27.
Zhang JM, Wang HK, Ye CQ, Ge W, Chen Y, Jiang ZL, and others. 2003. ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron40:971–982.
28.
Zhang Q, Fukuda M, Van Bockstaele E, Pascual O, Haydon PG. 2004. Synaptotagmin IV regulates glial glutamate release. Proc Natl Acad Sci U S A101:9441–9946.
29.
Zhou Z, Misler S. 1995. Action potential-induced quantal secretion of catecholamines from rat adrenal chromaffin cells. J Biol Chem270:3498–3505.
30.
Zhou Z, Misler S. 1996. Amperometric detection of quantal secretion from patch-clamped rat pancreatic beta-cells. J Biol Chem271:270–277.
31.
Zhou Z, Misler S, Chow RH. 1996. Rapid fluctuations in transmitter release from single vesicles in bovine adrenal chromaffin cells. Biophys J70:1543–1552.
