Abstract：
Two-trial learning in Aplysia reveals nonlinear interactions between training trials: A single trial has no effect, but two precisely spaced trials induce long-term memory. Extracellularly regulated kinase (ERK) activity is essential for intertrial interactions, but the mechanism remains unresolved. A combination of immunochemical and optogenetic tools reveals unexpected complexity of ERK signaling during the induction of long-term synaptic facilitation by two spaced pulses of serotonin (5-hydroxytryptamine, 5HT). Specifically, dual ERK phosphorylation at its activating TxY motif is accompanied by dephosphorylation at the pT position, leading to a buildup of inactive, singly phosphorylated pY-ERK. Phosphorylation and dephosphorylation occur concurrently but scale differently with varying 5HT concentrations, predicting that mixed two-trial protocols involving both \"strong\" and \"weak\" 5HT pulses should be sensitive to the precise order and timing of trials. Indeed, long-term synaptic facilitation is induced only when weak pulses precede strong, not vice versa. This may represent a physiological mechanism to prioritize memory of escalating threats.
摘要：
Aplysia中的两次试验学习揭示了训练试验之间的非线性相互作用：单个试验没有效果，但是两个精确间隔的试验会诱导长期记忆。细胞外调节激酶（ERK）活性对于试验间相互作用至关重要，但机制仍未解决。免疫化学和光遗传学工具的组合揭示了通过两个间隔的5-羟色胺脉冲（5-羟色胺，5HT)。具体来说,激活TxY基序的双ERK磷酸化伴随着pT位置的去磷酸化，导致不活跃的积累，单磷酸化pY-ERK。磷酸化和去磷酸化同时发生，但随着5HT浓度的变化而变化，预测涉及“强”和“弱”5HT脉冲的混合两次试验方案应该对试验的精确顺序和时间敏感。的确,只有弱脉冲先于强脉冲时，才能诱导长期突触促进，反之亦然。这可以代表一种生理机制来优先考虑升级威胁的记忆。
