The many ways astroglial connexins regulate neurotransmission and behavior

Astrocytes have emerged as major players in the brain, contributing to many functions such as energy supply, neurotransmission, and behavior. They accomplish these functions in part via their capacity to form widespread intercellular networks and to release neuroactive factors, which can modulate neurotransmission at different levels, from individual synapses to neuronal networks. The extensive network communication of astrocytes is primarily mediated by gap junction channels composed of two connexins, Cx30 and Cx43, which present distinct temporal and spatial expression patterns. Yet, astroglial connexins are also involved in direct exchange with the extracellular space via hemichannels, as well as in adhesion and signaling processes via unconventional nonchannel functions. Accumulating evidence indicate that astrocytes modulate neurotransmission and behavior through these diverse connexin functions. We here review the many ways astroglial connexins regulate neuronal activity from the molecular level to behavior.