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. 2021 Oct 12;15:706025. doi: 10.3389/fncel.2021.706025

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Copyright © 2021 Ding, Guo, Luo, Zheng, Gan, Kang, Wu and Zhu.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Communication between microglia and neurons. ATP can be secreted from neurons through vesicles or the pannexin-1 channel. Released ATP (red) is converted into ADP (yellow) by the microglial enzyme CD39. ADP acts on P₂RY₁₂ receptors to induce activation of P₂RY₁₂ signaling, which attracts microglial processes to synaptic connections. CD39 also converts ADP into AMP (green). Next, AMP is converted into ADO (pink) by the enzyme CD73 on microglia. ADO suppresses neuronal activity by acting on A₁Rs by decreasing glutamate (blue) release and inhibiting calcium (Ca²⁺) channels. In addition, A_2ARs can weaken the inhibitory effect of A1Rs on glutamate release. ATP = adenosine triphosphate, ADP = adenosine diphosphate, AMP = adenosine monophosphate, ADO = adenosine, A₁R = A₁ receptor, A_2AR = A_2A receptor.