Formation of temporal association memory and context-specific fear memory is thought to require medial entorhinal cortex (MEC) inputs to the hippocampus during learning events. However, whether the MEC inputs are also involved in memory formation during a post-learning period has not been directly tested yet. To examine this possibility, we optogenetically inhibited axons and terminals originating from bilateral dorsal MEC excitatory neurons in the dorsal hippocampus for 5 min right after contextual fear conditioning (CFC). Mice expressing eNpHR3.0 exhibited significantly less freezing compared to control mice expressing EGFP alone during retrieval test in the conditioned context 1 day after learning. In contrast, the same optogenetic inhibition of MEC inputs performed 30 min before retrieval test did not affect freezing during retrieval test, excluding the possibility of non-specific deleterious effect of optical inhibition on retrieval process. These results support that contextual fear memory formation requires MEC inputs to the hippocampus during a post-learning period.

中文翻译：

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学习后短时间内内侧内嗅皮层对海马体输入的光遗传学抑制会破坏情境恐惧记忆的形成


时间关联记忆和情境特定恐惧记忆的形成被认为需要学习事件期间内侧内嗅皮层（MEC）输入到海马体。然而，MEC 输入是否也参与学习后时期的记忆形成尚未得到直接测试。为了检验这种可能性，我们在情境恐惧条件反射 (CFC) 后立即通过光遗传学方法抑制来自背侧海马双侧背侧 MEC 兴奋性神经元的轴突和末梢 5 分钟。学习后 1 天的条件环境中的检索测试期间，与单独表达 EGFP 的对照小鼠相比，表达 eNpHR3.0 的小鼠表现出明显较少的冻结。相比之下，在检索测试前30分钟对MEC输入进行相同的光遗传学抑制不会影响检索测试期间的冻结，排除了光抑制对检索过程产生非特异性有害影响的可能性。这些结果支持情境恐惧记忆的形成需要在学习后阶段向海马体输入 MEC。