Endogenous nonneuronal modulators of synaptic transmission control cortical slow oscillations in vivo
- Tommaso Fellina,b,1,
- Michael M. Halassaa,
- Miho Terunumaa,c,
- Francesca Succola,b,
- Hajime Takanoa,
- Marcos Franka,
- Stephen J. Mossa,c and
- Philip G. Haydona,c
- aSilvio Conte Center for Integration at the Tripartite Synapse, Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104;
- bDepartment of Neuroscience and Brain Technologies, Italian Institute of Technology, 16163 Genova, Italy; and
- cDepartment of Neuroscience, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111
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Edited by Tullio Pozzan, University of Padua, Padua, Italy, and approved July 14, 2009 (received for review June 10, 2009)
Abstract
Gliotransmission, the release of molecules from astrocytes, regulates neuronal excitability and synaptic transmission in situ. Whether this process affects neuronal network activity in vivo is not known. Using a combination of astrocyte-specific molecular genetics, with in vivo electrophysiology and pharmacology, we determined that gliotransmission modulates cortical slow oscillations, a rhythm characterizing nonrapid eye movement sleep. Inhibition of gliotransmission by the expression of a dominant negative SNARE domain in astrocytes affected cortical slow oscillations, reducing the duration of neuronal depolarizations and causing prolonged hyperpolarizations. These network effects result from the astrocytic modulation of intracortical synaptic transmission at two sites: a hypofunction of postsynaptic NMDA receptors, and by reducing extracellular adenosine, a loss of tonic A1 receptor-mediated inhibition. These results demonstrate that rhythmic brain activity is generated by the coordinated action of the neuronal and glial networks.
Footnotes
- 1To whom correspondence should be addressed. E-mail: tommaso.fellin{at}iit.it
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Author contributions: T.F., M.M.H., and P.G.H. designed research; T.F., M.M.H., M.T., and F.S. performed research; M.F. and S.J.M. contributed new reagents/analytic tools; T.F., M.M.H., M.T., and H.T. analyzed data; and T.F., M.M.H., and P.G.H. wrote the paper.
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The authors declare no conflict of interest.
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This article is a PNAS Direct Submission.
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This article contains supporting information online at www.pnas.org/cgi/content/full/0906419106/DCSupplemental.
