Department of Neuroscience, Osaka University Graduate School of Frontier Biosciences, Osaka, Japan.
Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama-Gakuin University, Kanagawa, Japan.
Hippocampus. 2020 Jul;30(7):763-769. doi: 10.1002/hipo.23206. Epub 2020 Apr 22.
We have previously shown that repetitive induction of long-term potentiation (LTP) by glutamate (100 μM, 3 min, three times at 24-hr intervals) provoked long-lasting synaptic enhancement accompanied by synaptogenesis in rat hippocampal slice cultures, a phenomenon termed RISE (repetitive LTP-induced synaptic enhancement). Here, we examined the role of Ca -permeable (CP) AMPA receptors (AMPARs) in the establishment of RISE. We first found a component sensitive to the Joro-spider toxin (JSTX), a blocker of CP-AMPARs, in a field EPSP recorded from CA3-CA1 synapses at 2-3 days after stimulation, but this component was not found for 9-10 days. We also observed that rectification of AMPAR-mediated current appeared only 2-3 days after stimulation, using a whole-cell patch clamp recording from CA1 pyramidal neurons. These findings indicate that CP-AMPAR is transiently expressed in the developing phase of RISE. The blockade of CP-AMPARs by JSTX for 24 hr at this developing phase inhibited RISE establishment, accompanied by the loss of small synapses at the ultrastructural level. These results suggest that transiently induced CP-AMPARs play a critical role in synaptogenesis in the developing phase of long-lasting hippocampal synaptic plasticity, RISE.
我们之前已经证明，通过谷氨酸（100μM，3 分钟，24 小时间隔三次）重复诱导长时程增强（LTP）会引起大鼠海马切片培养中伴随突触发生的持久突触增强，这种现象称为 RISE（重复 LTP 诱导的突触增强）。在这里，我们研究了钙通透性（CP）AMPA 受体（AMPAR）在 RISE 建立中的作用。我们首先发现，在刺激后 2-3 天从 CA3-CA1 突触记录的场兴奋性突触后电位（EPSP）中存在对 Joro 蜘蛛毒素（JSTX）敏感的成分，JSTX 是 CP-AMPAR 的阻断剂，但在 9-10 天后未发现该成分。我们还观察到，在刺激后 2-3 天，使用 CA1 锥体神经元的全细胞贴片记录，出现了 AMPAR 介导的电流的整流。这些发现表明 CP-AMPAR 在 RISE 的发育阶段短暂表达。在发育阶段，用 JSTX 阻断 CP-AMPAR 24 小时会抑制 RISE 的建立，并伴有超微结构水平上小突触的丢失。这些结果表明，在长时程海马突触可塑性发育阶段的 RISE 中，短暂诱导的 CP-AMPAR 发挥了关键作用。
