Adenosine A1 Receptor-Mediated Synaptic Depression in the Developing Hippocampal Area CA2
Adenosine A1 Receptor-Mediated Synaptic Depression in the Developing Hippocampal Area CA2
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DOI：
10.3389/fnsyn.2020.00021
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发表时间：
2020-06-15
影响因子：
3.7
通讯作者：
Dudek, Serena M.
中科院分区：
文献类型：
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作者：
Caruana, Douglas A.;Dudek, Serena M.
在成年大鼠的海马区CA2区，腺苷A(1)受体(A(1)Rs)的免疫标记很高，咖啡因或其他A(1)R选择性拮抗剂对突触反应的增强作用在CA2的Schaffer侧支突触尤其强烈。有趣的是，CA2中A(1)Rs的明显染色直到4周大鼠才明显，这表明幼年动物CA2突触对A(1)R拮抗剂的敏感性是由受体分布以外的发育变化引起的。为了评估A(1)R介导的突触后信号在这些突触中的作用，我们测试了A(1)R激动剂是否调节CA2和CA1的Schaffer侧支输入的突触传递。我们发现选择性A(1)受体激动剂CCPA对幼年大鼠脑片CA2和CA1神经元的突触反应均有持久的抑制作用(P14)，但这种作用仅在成年动物脑片的CA2中观察到(与P70相似)。有趣的是，用罗利普兰阻断磷酸二酯酶活性可以抑制CCPA诱导的CA1的抑制，但不能抑制CA2的抑制，这表明CA1神经元中的磷酸二酯酶活性很强。同样，CA2和CA1的突触反应对腺酰环化酶激活剂Forsklin的敏感性不同，因为它增加了CA2的突触传递，但对CA1的影响很小。这些结果表明，A(1)R介导的突触抑制跟踪A(1)Rs免疫标记的出生后发展，年轻时对CA2拮抗剂的敏感性增强可能是由于强大的腺酰环化酶活性和弱的磷酸二酯酶活性，而不是由于A(1)Rs的丰富。
Immunolabeling for adenosine A(1) receptors (A(1)Rs) is high in hippocampal area CA2 in adult rats, and the potentiating effects of caffeine or other A(1)R-selective antagonists on synaptic responses are particularly robust at Schaffer collateral synapses in CA2. Interestingly, the pronounced staining for A(1)Rs in CA2 is not apparent until rats are 4 weeks old, suggesting that developmental changes other than receptor distribution underlie the sensitivity of CA2 synapses to A(1)R antagonists in young animals. To evaluate the role of A(1)R-mediated postsynaptic signals at these synapses, we tested whether A(1)R agonists regulate synaptic transmission at Schaffer collateral inputs to CA2 and CA1. We found that the selective A(1)R agonist CCPA caused a lasting depression of synaptic responses in both CA2 and CA1 neurons in slices obtained from juvenile rats (P14), but that the effect was observed only in CA2 in slices prepared from adult animals (similar to P70). Interestingly, blocking phosphodiesterase activity with rolipram inhibited the CCPA-induced depression in CA1, but not in CA2, indicative of robust phosphodiesterase activity in CA1 neurons. Likewise, synaptic responses in CA2 and CA1 differed in their sensitivity to the adenylyl cyclase activator, forskolin, in that it increased synaptic transmission in CA2, but had little effect in CA1. These findings suggest that the A(1)R-mediated synaptic depression tracks the postnatal development of immunolabeling for A(1)Rs and that the enhanced sensitivity to antagonists in CA2 at young ages is likely due to robust adenylyl cyclase activity and weak phosphodiesterase activity rather than to enrichment of A(1)Rs.