1. Astroglial hemichannels modulate UP and DOWN states in the olfactory bulb.
- Author
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Roux, L., Madar, A., Lacroix, M., Benchenane, K., and Giaume, C.
- Subjects
ASTROCYTES ,CONNEXINS ,GAP junctions (Cell biology) - Abstract
While the role played by astrocytes in synaptic transmission has now largely been documented, their contribution to network activities only starts to be appreciated. A typical feature of astrocytes is their high rate of connexin expression (Cx43 and Cx30), the molecular basis for gap junctional communication and hemichannel (HC) formation. Even though connexin-formed HCs have been shown to be permeable to several neuroactive compounds, their role in physiological conditions has largely been unexplored. We thus question whether the function of Cx-based HCs in astrocytes has an impact on neuronal network behaviors in the mouse olfactory bulb (OB). In OB acute slices, we observed that the membrane potential of mitral cells (MCs) alternates between a DOWN (hyperpolarized, silent) and an UP (depolarized, spiking) state at a slow frequency (~0.2Hz), resembling slow oscillations observed in cortical neurons during slow-wave sleep. Such alternations were inhibited by a pharmalogical blockage of glutamatergic transmission and correlated with the local field potential monitored within the corresponding glomerulus, highlighting a network effect. Interestingly, this spontaneous neuronal activity induced the opening of Cx HCs in astrocytes as shown by ethidium bromide uptake assays. We then asked whether such astroglial HC activity can in turn impact on the slow network activity, using knock-out (KO) mice for astroglial Cxs. In absence of Cx43, but not Cx30, MCs showed significant decrease in UP state amplitude compared to control. This alteration was mimicked by a blockage of Cx43 HCs, pointing out the role played by Cx43 HC function in the modulation of MC UP and DOWN states. Importantly, we found that this effect requires the activation of adenosine A1 receptors, likely via ATP release by astrocytes through Cx43 HCs. These results suggest that Cx43 HC function in astrocytes is promoted by neuronal activity, and in turn modulates neuronal network activity. Such bidirectional neuroglial interactions could play an important role in olfactory information processing. [ABSTRACT FROM AUTHOR]
- Published
- 2013