During development, neural circuit formation requires the stabilization of active γ-aminobutyric acid–mediated (GABAergic) synapses and the elimination of inactive ones. Here, we demonstrate that, although the activation of postsynaptic GABA type A receptors (GABA_ARs) and adenosine A_2A receptors (A_2ARs) stabilizes GABAergic synapses, only A_2AR activation is sufficient. Both GABA_AR- and A_2AR-dependent signaling pathways act synergistically to produce adenosine 3′,5′-monophosphate through the recruitment of the calcium–calmodulin–adenylyl cyclase pathway. Protein kinase A, thus activated, phosphorylates gephyrin on serine residue 303, which is required for GABA_AR stabilization. Finally, the stabilization of pre- and postsynaptic GABAergic elements involves the interaction between gephyrin and the synaptogenic membrane protein Slitrk3. We propose that A_2ARs act as detectors of active GABAergic synapses releasing GABA, adenosine triphosphate, and adenosine to regulate their fate toward stabilization or elimination.

中文翻译：

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腺苷和 GABA 信号在发育过程中稳定突触的收敛

在发育过程中，神经回路的形成需要稳定活跃的 γ-氨基丁酸介导的（GABA 能）突触并消除不活跃的突触。在这里，我们证明，虽然突触后 GABA A 型受体 (GABA _A Rs) 和腺苷 A _2A受体 (A _2A Rs) 的激活稳定了 GABA 能突触，但只有 A _2A R 激活就足够了。GABA _A R 和 A _2A R 依赖性信号通路通过募集钙-钙调蛋白-腺苷酸环化酶途径协同作用产生 3',5'-单磷酸腺苷。因此激活的蛋白激酶 A 磷酸化 303 位丝氨酸残基上的 gephyrin，这是 GABA _{A所必需的}R 稳定。最后，突触前和突触后 GABA 能元件的稳定涉及 gephyrin 和突触膜蛋白 Slitrk3 之间的相互作用。我们建议 A _2A Rs 充当释放 GABA、三磷酸腺苷和腺苷的活性 GABA 能突触的检测器，以调节其稳定或消除的命运。