Astroglial Connexin 43 Hemichannels Modulate Olfactory Bulb Slow Oscillations.

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. SIGNIFICANCE STATEMENT: 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.