Astrocytes mediate Short‐term Plasticity of Breathing

Abstract

Respiratory plasticity contributes to stabilization of ventilation. However, its cellular mechanism has not been clarified. We hypothesized that astrocytes mediate respiratory plasticity, based on the discovery that astrocytes are actively involved in neural plasticity in various brain functions. To examine our hypothesis, we analyzed the effects of ONO‐2506, an inhibitor of astrocytic activation, on post‐hypoxic short‐term potentiation of breathing. Ventilatory parameters of unanesthetized adult mice were measured by whole body plethysmography (n=11). To test the hypoxic response, mice breathed room air, then hypoxic gas (7% O2, 93% N2), and again room air. After recording control hypoxic response with recovery time course, low and high doses of ONO‐2506 was ip injected. Although ONO‐2506 little affected ventilatory augmentation during hypoxic loading, it suppressed post‐stimulus potentiation of breathing. High dose ONO‐2506 completely eliminated post‐stimulus potentiation. We conclude that post‐stimulus potentiation of breathing is mediated by astrocytes. We propose a model to explain the mechanism of post‐hypoxic potentiation. Hypoxia stimulates the respiratory neuronal network through the excitation of the carotid body. Neurotransmitters spilled from excited synapses activate nearby astrocytes. These activated astrocytes persistently excite respiratory neuronal network by continuously releasing gliotransmitters, and short‐term respiratory plasticity emerges.