To determine the critical timing for learning and the associated synaptic plasticity, we analyzed developmental changes in learning together with training-induced plasticity. Rats were subjected to an inhibitory avoidance (IA) task prior to weaning. While IA training did not alter latency at postnatal day (PN) 16, there was a significant increase in latency from PN 17, indicating a critical day for IA learning between PN 16 and 17. One hour after training, acute hippocampal slices were prepared for whole-cell patch clamp analysis following the retrieval test. In the presence of tetrodotoxin (0.5 µM), miniature excitatory postsynaptic currents (mEPSCs) and inhibitory postsynaptic currents (mIPSCs) were sequentially recorded from the same CA1 neuron. Although no changes in the amplitude of mEPSCs or mIPSCs were observed at PN 16 and 21, significant increases in both excitatory and inhibitory currents were observed at PN 23, suggesting a specific critical day for training-induced plasticity between PN 21 and 23. Training also increased the diversity of postsynaptic currents at PN 23 but not at PN 16 and 21, demonstrating a critical day for training-induced increase in the information entropy of CA1 neurons. Finally, we analyzed the plasticity at entorhinal cortex layer III (ECIII)-CA1 or CA3-CA1 synapses for each individual rat. At either ECIII-CA1 or CA3-CA1 synapses, a significant correlation between mean α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/N-methyl-D-aspartic acid (AMPA/NMDA) ratio and learning outcomes emerged at PN 23 at both synapses, demonstrating a critical timing for the direct link between AMPA receptor-mediated synaptic plasticity and learning efficacy. Here, we identified multiple critical periods with respect to training-induced synaptic plasticity and delineated developmental trajectories of learning mechanisms at hippocampal CA1 synapses.

中文翻译：

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海马 CA1 突触突触可塑性的出生后发育：学习表现与通路特异性可塑性的相关性

为了确定学习的关键时机和相关的突触可塑性，我们分析了学习的发展变化以及训练引起的可塑性。大鼠在断奶前接受抑制性回避（IA）任务。虽然 IA 训练没有改变出生后第 16 天 (PN) 的潜伏期，但与 PN 17 相比，潜伏期显着增加，表明 PN 16 和 17 之间是 IA 学习的关键日。训练一小时后，准备急性海马切片检索测试后进行全细胞膜片钳分析。在河豚毒素 (0.5 µM) 存在的情况下，从同一 CA1 神经元依次记录微型兴奋性突触后电流 (mEPSC) 和抑制性突触后电流 (mIPSC)。尽管在 PN 16 和 21 时没有观察到 mEPSC 或 mIPSC 振幅的变化，但在 PN 23 时观察到兴奋性和抑制电流显着增加，这表明 PN 21 和 23 之间是训练诱导可塑性的特定关键日。增加了 PN 23 处突触后电流的多样性，但没有增加 PN 16 和 21 处的突触后电流多样性，这表明训练诱导的 CA1 神经元信息熵增加的关键一天。最后，我们分析了每只大鼠的内嗅皮层 III 层 (ECIII)-CA1 或 CA3-CA1 突触的可塑性。在 ECIII-CA1 或 CA3-CA1 突触中，平均 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/N-甲基-D-天冬氨酸 (AMPA/NMDA) 比率与学习之间存在显着相关性结果在 PN 23 时在两个突触处出现，证明了 AMPA 受体介导的突触可塑性和学习效能之间直接联系的关键时机。在这里，我们确定了训练引起的突触可塑性的多个关键时期，并描绘了海马 CA1 突触学习机制的发展轨迹。