The hippocampus plays an essential role in the formation and retrieval of episodic memories in humans and contextual memories in animals. However, amnesia is not always observed when this structure is compromised. To determine why this is the case, we compared the effects of several different circuit manipulations on memory retrieval and hippocampal activity. Mice were first trained on context fear conditioning and then optogenetic and chemogenetic tools were used to alter activity during memory retrieval. We found that retrieval was only impaired when manipulations caused widespread changes (increases or decreases) in hippocampal activity. Widespread increases occurred when pyramidal cells were excited and widespread decreases were found when GABAergic neurons were stimulated. Direct hyperpolarization of excitatory neurons only moderately reduced activity and did not produce amnesia. Surprisingly, widespread decreases in hippocampal activity did not prevent retrieval if they occurred gradually prior to testing. This suggests that intact brain regions can express contextual memories if they are given adequate time to compensate for the loss of the hippocampus.

海马在人类情景记忆和动物情境记忆的形成和检索中发挥着重要作用。然而，当这种结构受到破坏时，并不总是观察到健忘症。为了确定为什么会这样，我们比较了几种不同的电路操作对记忆检索和海马活动的影响。首先对小鼠进行情境恐惧条件反射训练，然后使用光遗传学和化学遗传学工具来改变记忆检索过程中的活动。我们发现，只有当操作导致海马活动发生广泛变化（增加或减少）时，检索才会受损。当锥体细胞被兴奋时会出现广泛的增加，而当 GABA 能神经元受到刺激时会出现广泛的减少。兴奋性神经元的直接超极化仅适度降低活动并且不产生健忘症。令人惊讶的是，如果海​​马活动在测试前逐渐发生，海马活动的广泛减少并不能阻止恢复。这表明，如果给予足够的时间来弥补海马体的损失，完整的大脑区域可以表达上下文记忆。