Astrocytes tune neuronal excitability through the Ca2+-activated K+current sIAHP

Abstract

SUMMARYNeurons have the unique ability to integrate synaptic information by modulating the function of the voltage-gated membrane ion channels, which govern their excitability. Astrocytes play active roles in synaptic function, from synapse formation and maturation to plasticity processes. However, it remains elusive whether astrocytes can impact the neuronal activity by regulating membrane ion conductances that control the intrinsic firing properties. Here, we found that astrocytes, by releasing adenosine, enhance the slow Ca2+-activated K+current (sIAHP) in CA1 hippocampal pyramidal neurons. Remarkably, we showed that interneuron activity was involved in the astrocyte-mediated sIAHP modulation. Indeed, both synaptically activated and optogenetically stimulated hippocampal interneurons evoked coordinated signaling in astrocytes and pyramidal neurons, which relied on GABABand adenosine A1 receptors activation. In addition, the selective genetic ablation of GABABreceptors in CA1 astrocytes prevented the spike frequency adaptation in pyramidal cells after interneuron activation. Therefore, our data reveal the astrocyte capability to modulate the intrinsic membrane properties that dictate neuronal firing rate and hippocampal networks activity.