Protein phosphatase-dependent circadian regulation of intermediate-term associative memory.
Protein phosphatase-dependent circadian regulation of intermediate-term associative memory.
复制标题
DOI：
10.1523/jneurosci.4534-12.2013
复制
发表时间：
2013-03-06
期刊：
影响因子：
--
通讯作者：
Lyons LC
中科院分区：
文献类型：
--
作者：
Michel M;Gardner JS;Green CL;Organ CL;Lyons LC
内源性生物钟是调节物种记忆的主要因素。确定生物钟调节记忆形成的过程是理解和识别改善记忆机制的关键问题。我们使用的海洋软体动物Aaplasia californica调查昼夜节律调制的中期记忆（ITM）和机制，通过生物钟相位具体抑制记忆使用操作学习范式，学习食物是不可食用的。我们发现，ITM，一个时间和机械不同形式的记忆，是有节奏地表达在明暗和恒定的条件下，无论是大规模或间隔训练诱导。强烈的昼夜节律调节ITM发生与记忆表现出的动物训练期间，在主观的早期一天，没有明显的记忆表示，当训练发生在主观的后期白天或夜晚。鉴于ITM的多个持续性激酶级联的必要性，我们研究了蛋白磷酸酶活性是否影响昼夜节律调节。抑制蛋白磷酸酶1和2A阻断ITM时，动物在早期（主观）的一天，而导致在特定阶段的记忆救援时，动物在主观的白天和深夜训练。相比之下，抑制钙调神经磷酸酶没有阻止ITM时，动物在白天早些时候训练，允许ITM时，动物在主观的一天，傍晚和整个晚上训练。这些结果表明，蛋白磷酸酶活性水平是ITM的关键调节因子，也是生物钟调节记忆形成的一种机制。
The endogenous circadian clock is a principal factor modulating memory across species. Determining the processes through which the circadian clock modulates memory formation is a key issue in understanding and identifying mechanisms to improve memory. We used the marine mollusk Aplysia californica to investigate circadian modulation of intermediate-term memory (ITM) and the mechanisms through which the circadian clock phase specifically suppresses memory using the operant learning paradigm, learning that food is inedible. We found that ITM, a temporally and mechanistically distinct form of memory, is rhythmically expressed under light-dark and constant conditions when induced by either massed or spaced training. Strong circadian regulation of ITM occurs with memory exhibited only by animals trained during the early subjective day; no apparent memory is expressed when training occurs during the late subjective day or night. Given the necessity of multiple persistent kinase cascades for ITM, we investigated whether protein phosphatase activity affected circadian modulation. Inhibition of protein phosphatases 1 and 2A blocked ITM when animals were trained during the early (subjective) day while resulting in phase-specific memory rescue when animals were trained late in the subjective day and early night. In contrast, inhibition of calcineurin did not block ITM when animals were trained during the early day and permitted ITM when animals were trained during the late subjective day, early evening and throughout the night. These results demonstrate that levels of protein phosphatase activity are critical regulators of ITM and one mechanism through which the circadian clock regulates memory formation.