CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal.
Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3004-504 Coimbra, Portugal.
Biomolecules. 2023 Apr 21;13(4):715. doi: 10.3390/biom13040715.
Adenosine operates a modulation system fine-tuning the efficiency of synaptic transmission and plasticity through A and A receptors (AR, AR), respectively. Supramaximal activation of AR can block hippocampal synaptic transmission, and the tonic engagement of AR-mediated inhibition is increased with increased frequency of nerve stimulation. This is compatible with an activity-dependent increase in extracellular adenosine in hippocampal excitatory synapses, which can reach levels sufficient to block synaptic transmission. We now report that AR activation decreases AR-medated inhibition of synaptic transmission, with particular relevance during high-frequency-induced long-term potentiation (LTP). Thus, whereas the AR antagonist DPCPX (50 nM) was devoid of effects on LTP magnitude, the addition of an AR antagonist SCH58261 (50 nM) allowed a facilitatory effect of DPCPX on LTP to be revealed. Additionally, the activation of AR with CGS21680 (30 nM) decreased the potency of the AR agonist CPA (6-60 nM) to inhibit hippocampal synaptic transmission in a manner prevented by SCH58261. These observations show that AR play a key role in dampening AR during high-frequency induction of hippocampal LTP. This provides a new framework for understanding how the powerful adenosine AR-mediated inhibition of excitatory transmission can be controlled to allow the implementation of hippocampal LTP.
腺苷通过 A 和 A 受体（AR，AR）分别操作一个调制系统，精细调节突触传递和可塑性的效率。AR 的超刺激可阻断海马突触传递，并且随着神经刺激频率的增加，AR 介导的抑制的紧张参与增加。这与海马兴奋性突触中细胞外腺苷的活动依赖性增加是一致的，细胞外腺苷可达到足以阻断突触传递的水平。我们现在报告 AR 的激活可降低 AR 介导的突触传递抑制，在高频诱导的长时程增强（LTP）期间尤其相关。因此，虽然 AR 拮抗剂 DPCPX（50 nM）对 LTP 幅度没有影响，但添加 AR 拮抗剂 SCH58261（50 nM）可揭示 DPCPX 对 LTP 的促进作用。此外，用 CGS21680（30 nM）激活 AR 以降低 AR 激动剂 CPA（6-60 nM）抑制海马突触传递的效力，SCH58261 可阻止这种降低。这些观察结果表明，AR 在高频诱导海马 LTP 期间在抑制 AR 方面发挥关键作用。这为理解如何控制强大的腺苷 AR 介导的兴奋性传递抑制以允许实施海马 LTP 提供了一个新的框架。
