title: Astroglial Connexin 43 Hemichannels Modulate Olfactory Bulb Slow Oscillations.
abstract: An emergent concept in neurosciences consists in considering brain functions as the product of dynamic interactions between neurons and glial cells, particularly astrocytes. Although the role played by astrocytes in synaptic transmission and plasticity is now largely documented, their contribution to neuronal network activity is only beginning to be appreciated. In mouse olfactory bulb slices, we observed that the membrane potential of mitral cells oscillates between UP and DOWN states at a low frequency (<1 Hz). Such slow oscillations are correlated with glomerular local field potentials, indicating spontaneous local network activity. Using a combination of genetic and pharmacological tools, we showed that the activity of astroglial connexin 43 hemichannels, opened in an activity-dependent manner, increases UP state amplitude and impacts mitral cell firing rate. This effect requires functional adenosine A1 receptors, in line with the observation that ATP is released via connexin 43 hemichannels. These results highlight a new mechanism of neuroglial interaction in the olfactory bulb, where astrocyte connexin hemichannels are both targets and modulators of neuronal circuit function.
  
  
  CONCLUSIONS
  An emergent concept in neuroscience consists in considering brain function as the product of dynamic interactions between neurons and glial cells, particularly astrocytes. A typical feature of astrocytes is their high expression level of connexins, the molecular constituents of gap junction channels and hemichannels. Although hemichannels represent a powerful medium for intercellular communication between astrocytes and neurons, their function in physiological conditions remains largely unexplored. Our results show that in the olfactory bulb, connexin 43 hemichannel function is promoted by neuronal activity and, in turn, modulates neuronal network slow oscillations. This novel mechanism of neuroglial interaction could influence olfactory information processing by directly impacting the output of the olfactory bulb.
authors.affiliation: Center for Interdisciplinary Research in Biology, Collège de France/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241, Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, France, University Pierre et Marie Curie, 75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France.
authors.forename: Lisa
authors.initials: L
authors.lastname: Roux
authors.affiliation: Center for Interdisciplinary Research in Biology, Collège de France/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241, Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, France, University Pierre et Marie Curie, 75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Madar
authors.affiliation: Memory Oscillations and Brain States Team, Laboratory of Neurobiology, Brain Plasticity Unit, Unité Mixte de Recherche 8249, CNRS, Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris - ParisTech, 75005 Paris, France.
authors.forename: Marie Masako
authors.initials: MM
authors.lastname: Lacroix
authors.affiliation: Center for Interdisciplinary Research in Biology, Collège de France/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241, Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, France, University Pierre et Marie Curie, 75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France.
authors.forename: Chenju
authors.initials: C
authors.lastname: Yi
authors.affiliation: Memory Oscillations and Brain States Team, Laboratory of Neurobiology, Brain Plasticity Unit, Unité Mixte de Recherche 8249, CNRS, Ecole Supérieure de Physique et de Chimie Industrielles de la Ville de Paris - ParisTech, 75005 Paris, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Benchenane
authors.affiliation: Center for Interdisciplinary Research in Biology, Collège de France/Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7241, Institut National de la Santé et de la Recherche Médicale U1050, 75231 Paris Cedex 05, France, University Pierre et Marie Curie, 75005 Paris, France, MemoLife Laboratory of Excellence and Paris Science Lettre Research University, 75005 Paris, France, christian.giaume@college-de-france.fr.
authors.forename: Christian
authors.initials: C
authors.lastname: Giaume
mesh_terms: D058916:Adenosine A1 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D001683:Biological Clocks / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002229:Carbenoxolone / Q000494:pharmacology; D000075302:Connexin 30; D018031:Connexin 43 / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000172:deficiency / Q000235:genetics; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009830:Olfactory Bulb / Q000166:cytology* / Q000502:physiology*; D010455:Peptides / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D013779:Tetrodotoxin / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058916:Adenosine A1 Receptor Antagonists; D000075302:Connexin 30; D018031:Connexin 43; D017630:Connexins; C514423:Gap 26 peptide; C100629:Gjb6 protein, mouse; D010455:Peptides; D026941:Sodium Channel Blockers; D014970:Xanthines; D018698:Glutamic Acid; D013779:Tetrodotoxin; C051360:1,3-dipropyl-8-cyclopentylxanthine; D002229:Carbenoxolone
keywords: DOWN state; UP state; astrocyte; hemichannel; mitral cells; olfactory glomeruli