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Roux L.,The Interdisciplinary Center | Roux L.,University Pierre and Marie Curie | Roux L.,MemoLife Laboratory of Excellence and Paris Science Lettre Research University | Madar A.,The Interdisciplinary Center | And 10 more authors.
Journal of Neuroscience | Year: 2015

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. © 2015 the authors.

Boulay A.-C.,The Interdisciplinary Center | Boulay A.-C.,University Pierre and Marie Curie | Boulay A.-C.,MemoLife Laboratory of Excellence and Paris Science Lettre Research University | Mazeraud A.,Institute Pasteur Paris | And 40 more authors.
Journal of Neuroscience | Year: 2015

In the normal brain, immune cell trafficking and immune responses are strictly controlled and limited. This unique homeostatic equilibrium, also called brain immune quiescence, is crucial to maintaining proper brain functions and is altered in various pathological processes, from chronic immunopathological disorders to cognitive and psychiatric impairments. To date, the precise nature of factors regulating the brain/immune system interrelationship is poorly understood. In the present study, we demonstrate that one of these regulating factors is Connexin 43 (C×43), a gap junction protein highly expressed by astrocytes at the blood- brain barrier (BBB) interface. We show that, by setting the activated state of cerebral endothelium, astroglial C×43 controls immune recruitment as well as antigen presentation mechanisms in the mouse brain. Consequently, in the absence of astroglial C×43, recruited immune cells elaborate a specific humoral autoimmune response against the von Willebrand factor A domain-containing protein 5a, an extracellular matrix protein of the brain. Altogether, our results demonstrate that C×43 is a new astroglial factor promoting the immune quiescence of the brain. © 2015 the authors.

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