Dentate Gyrus Contributes to Retrieval as well as Encoding: Evidence from Context Fear Conditioning, Recall, and Extinction
Dentate Gyrus Contributes to Retrieval as well as Encoding: Evidence from Context Fear Conditioning, Recall, and Extinction
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DOI：
10.1523/jneurosci.3029-16.2017
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发表时间：
2017-06-28
影响因子：
5.3
通讯作者：
Drew, Michael R.
中科院分区：
文献类型：
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作者：
Bernier, Brian E.;Lacagnina, Anthony F.;Drew, Michael R.
齿状回（DG）被广泛认为提供了一个教学信号，使海马编码的记忆，但其作用在检索知之甚少。一些数据和模型表明DG在提取中没有作用;另一些则鼓励相反的结论。为了解决这一争议，我们评估了雄性小鼠在背景恐惧条件反射、回忆、泛化和消退过程中背侧DG的光遗传学抑制的影响。结果发现：（1）训练时的抑制会损害情境恐惧的获得;（2）回忆时的抑制不会损害训练情境中的恐惧表达，除非小鼠必须区分相似的恐惧情境和中性情境;（3）在条件情境中，抑制会增加恐惧对与恐惧情境相似的陌生情境的泛化，而在与中性情境相似的条件情境中，抑制会损害恐惧表达;（4）抑制恐惧消退。这些影响，以及几个看似矛盾的已发表的研究结果，可以重现BACON（贝叶斯上下文恐惧算法），一个生理上现实的海马模型，假定收购和检索都涉及协调活动DG和CA 3。因此，我们的研究结果表明，DG有助于检索和灭绝，以及最初建立的背景恐惧。
Dentate gyrus (DG) is widely thought to provide a teaching signal that enables hippocampal encoding of memories, but its role during retrieval is poorly understood. Somedata and models suggest thatDGplays no role in retrieval; others encourage the opposite conclusion. To resolve this controversy, we evaluated the effects of optogenetic inhibition of dorsal DG during context fear conditioning, recall, generalization, and extinction in male mice. Wefound that (1) inhibition during training impaired context fear acquisition; (2) inhibition during recall did not impair fear expression in the training context, unless mice had to distinguish between similar feared and neutral contexts; (3) inhibition increased generalization of fear to an unfamiliar context that was similar to a feared one and impaired fear expression in the conditioned context when it was similar to a neutral one; and (4) inhibition impaired fear extinction. These effects, as well as several seemingly contradictory published findings, could be reproduced by BACON (Bayesian Context Fear Algorithm), a physiologically realistic hippocampal model positing that acquisition and retrieval both involve coordinated activity in DG and CA3. Our findings thus suggest that DG contributes to retrieval and extinction, as well as to the initial establishment of context fear.