Astroglial gap junctions strengthen hippocampal network activity by sustaining afterhyperpolarization via KCNQ channels

Abstract

Throughout the brain, astrocytes form networks mediated by gap-junction channels that promote the activity of neuronal ensembles. Although their inputs on neuronal information processing are well established, how molecularly gap junction channels shape neuronal network patterns remains unclear. Here using astroglial connexin-deficient mice, in which astrocytes are disconnected and neuronal bursting patterns are abnormal, we found that astrocyte networks strengthen bursting activity via dynamic regulation of extracellular potassium levels, independently of glutamate homeostasis or metabolic support. Using a novel facilitation-depression model, we identified neuronal afterhyperpolarization as the key parameter underlying bursting patterns regulation by extracellular potassium in mice with disconnected astrocytes. We confirmed experimentally this prediction, and revealed that astroglial network-control of extracellular potassium sustains neuronal afterhyperpolarization via activation of KCNQ voltage-gated K+ channels. Altogether, these data delineate how astroglial gap-junctions mechanistically strengthen neuronal population bursts, and points to approaches for controlling aberrant activity in neurological diseases.