Citations 2
Astrocyte-to-microglia purinergic signaling mediates synaptic shielding and promotes neuronal activity
Haruwaka, Koichiro , Liu, Juan , Liang, Yue, Matsumoto, Shinya , Shi, Wu, Zhao, Shunyi, Xie, Zhongcong, Jing, Miao, Wu, Long-Jun , Haruwaka, Koichiro , Kleidonas, Dimitrios , Liu, Yong , Umpierre, Anthony D. , Jing, Miao , Wu, Long‐Jun
No container title available | July 6, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract How glial cells sense and regulate neuronal hypoactivity remains poorly understood. Using in vivo imaging in anesthetized, sleeping, and behaving mice, we identified a glial purinergic signaling mechanism that converts neuronal hypoactivity into local circuit regulation. Cortical hypoactivity increased spatially confined ATP release through astrocytic pannexin-1 hemichannels, which were structurally enriched near perisomatic parvalbumin-positive boutons. Local ATP release directed microglial process movement and stabilized bulbous endings through microglial P2Y12 signaling, accompanied by localized Ca²⁺ activity in microglial processes. Disruption of astrocytic pannexin-1 or microglial P2Y12 impaired bulbous-ending stabilization and abolished rebound increases in neuronal activity during emergence from anesthesia. Similar ATP release and bulbous-ending formation were observed during chemogenetic neuronal silencing or natural sleep in freely behaving mice. These findings identify astrocyte-to-microglia purinergic signaling as a mechanism that converts neuronal hypoactivity into synapse-selective microglial regulation of circuit activity.
Cortical microglia promote noradrenergic signaling to maintain wakefulness
Liang, Yue , Shi, Wu, Dale, Emily M, Zhao, Shunyi, Qi, Fangfang, Haruwaka, Koichiro , Hou, Qixiu , Fei, Mengdi, Harris, Lauren , Hua, Xiaoyang, Wu, Long-jun, Dale, Emily M., Harris, Lauren
No container title available | December 27, 2025 | Volume: No volume available | Issue: No issue available | Pages: No page available
Abstract Microglia are essential for maintaining brain homeostasis, including the sleep-wake cycle, but the underlying mechanisms remain unclear. Here, using in vivo two-photon imaging in both head-fixed and freely moving mice with simultaneous electroencephalogram–electromyogram (EEG–EMG) recording, we investigated microglial process dynamics and their interactions with locus coeruleus (LC) noradrenergic (NE) axons in the frontal cortex across sleep-wake states. During sleep or chemogenetic suppression of LC neurons, microglia enhanced their surveillance and increased interactions with NE axons. Correlative electron microscopy at nanometer resolution identified structural contacts between microglial process endings and NE boutons. Mechanistically, microglia-bouton interaction is primed by NE–β2-adrenergic receptor (β2AR) signaling, leading to enhanced Ca²⁺ activity in NE axons. These findings suggest that microglial interactions with NE axons promote cortical norepinephrine transmission and maintain stable wakefulness.