3-B-P-030 〇坂井 謙斗¹、繁冨 英治^1,2、小泉 修一^1,2 Sakai Kent¹, Eiji Shigetomi^1,2, Schuichi Koizumi^{1,2 1}山梨大・院医・山梨GLIAセンター、²山梨大・院医・薬理 ¹Yamanashi GLIA center, Interdisciplinary Graduate School of Medicine, University of Yamanashi, ²Department of Neuropharmacology, Interdisciplinary Graduate School of Medicine, University of Yamanashi Adenosine (ADO) controls neuronal excitability in memory and sleep. Major sources of extracellular ADO (ADOo) are thought to be through the degradation of extracellular ATP and/or direct release from neurons and astrocytes. However, it is still unclear which cell regulates ADOo in physiology. To answer the question, we visualized the spatiotemporal dynamics of ADOo by using an ADO sensor, GRAB_ADO, in acute brain slices. Schaffer collateral electrical stimulation (E-stim) elevated ADO_o level in hippocampal CA1 region. The ADOo elevation by E-stim was abolished by treatment with TTX, silencing neuronal activity. Interestingly, the E-stim-induced elevation of ADOo was also abolished in brain slices from PLX 5622-fed mice, in which microglia were depleted. To clarify how neurons and microglia orchestrate ADOo level, we assessed several inhibitors. CNQX and D-AP5, antagonists of ionotropic glutamate receptors, reduced the elevation of ADOo by E-stim. In addition, treatment with JMS-17-2, a CX3CR1 inhibitor, reduced the elevation of ADOo induced by E-stim, and treatment with CX3CL1 increased ADOo. These data suggest that E-stim induces the release of CX3CL1 from postsynaptic neurons via the glutamate pathway between pre- and post-synaptic neurons, which leads to ADO release from microglia via the CX3CL1-CX3CR1 axis.