Unidad de Neurología Experimental, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, 28034, Spain.
Servicio de Neurobiología-Investigación, Hospital Universitario Ramón y Cajal, IRYCIS, Madrid, 28034, Spain.
Neuropharmacology. 2019 Jan;144:9-18. doi: 10.1016/j.neuropharm.2018.10.017. Epub 2018 Oct 13.
Recent studies have underscored the importance of the CA2 area in social memory formation. This area, a narrow transition zone between hippocampal CA3 and CA1 areas, is endowed with special connectivity and a distinctive molecular composition. In particular, adenosine A receptors (AR) are enriched in CA2, and based on the prominent synaptic potentiation induced by AR antagonists (e.g., caffeine) in this area, it has been proposed that CA2 is under the strong tonic control of AR activation. It is unclear whether this special sensitivity of CA2 to AR antagonists is due to an elevated extracellular concentration of adenosine or to a different AR function. Here, using the recording of field potentials evoked simultaneously in CA2 and CA1 by Schaffer collateral stimulation, we confirm that the application of AR antagonists, caffeine and DPCPX has a stronger effect on synaptic responses in CA2 than in those evoked in CA1. This difference was, at least partially, explained by the action of AR antagonists on presynaptic ARs. We found that caffeine-induced potentiation in CA2 was restricted to Schaffer collateral synapses, but not to those formed by temporoammonic inputs. We also observed that the apparent affinity of an AR agonist is similar for AR in both CA2 and CA1 areas, which indicates that the tonic activation of AR in both areas is comparable. Furthermore, we show that the direct activation of adenylyl cyclase with forskolin in the presence of rolipram, a phosphodiesterase inhibitor, greatly enhances the synaptic potentials in CA2 compared to CA1. The forskolin-induced potentiation was exacerbated in the presence of caffeine or DPCPX, accentuating the differences between the two areas. These results indicate that the tonic activation of ARs in area CA2 is not different to that of other hippocampal areas, but it is more efficiently coupled to the downstream effectors.
最近的研究强调了 CA2 区域在社会记忆形成中的重要性。这个区域是海马 CA3 和 CA1 区域之间的狭窄过渡带，具有特殊的连接和独特的分子组成。特别是，腺苷 A 受体（AR）在 CA2 中丰富，并且基于 AR 拮抗剂（例如咖啡因）在该区域诱导的明显突触增强，已经提出 CA2 受到 AR 激活的强烈紧张控制。尚不清楚 CA2 对 AR 拮抗剂的这种特殊敏感性是由于细胞外腺苷浓度升高还是由于不同的 AR 功能。在这里，我们使用 Schaffer 侧支刺激同时在 CA2 和 CA1 中记录场电位，证实 AR 拮抗剂咖啡因和 DPCPX 的应用对 CA2 中的突触反应的影响强于 CA1 中的突触反应。这种差异至少部分解释了 AR 拮抗剂对突触前 AR 的作用。我们发现，咖啡因诱导的 CA2 中的增强作用仅限于 Schaffer 侧支突触，但不限于由颞极输入形成的突触。我们还观察到，AR 激动剂的表观亲和力在 CA2 和 CA1 区域的 AR 相似，这表明两个区域的 AR 紧张激活相当。此外，我们表明，在 rolipram（一种磷酸二酯酶抑制剂）存在下，用 forskolin 直接激活腺苷酸环化酶会大大增强 CA2 中的突触电位，而不是 CA1 中的突触电位。在存在咖啡因或 DPCPX 的情况下，forskolin 诱导的增强作用加剧，突出了两个区域之间的差异。这些结果表明，CA2 区域中 AR 的紧张激活与其他海马区域没有不同，但与下游效应器的耦合效率更高。
