Puhger Kyle, Crestani Ana P, Diniz Cassiano R A F, Wiltgen Brian J
Department of Psychology, University of California, Davis, 135 Young Hall, 1 Shields Avenue, Davis, CA 95616, USA.
Center for Neuroscience, University of California, Davis, 1544 Newton Court, Davis, CA 95618, USA.
iScience. 2024 Jan 26;27(3):109035. doi: 10.1016/j.isci.2024.109035. eCollection 2024 Mar 15.
Binding events that occur at different times are essential for memory formation. In trace fear conditioning, animals associate a tone and footshock despite no temporal overlap. The hippocampus is thought to mediate this learning by maintaining a memory of the tone until shock occurrence, however, evidence for sustained hippocampal tone representations is lacking. Here, we demonstrate a retrospective role for the hippocampus in trace fear conditioning. Bulk calcium imaging revealed sustained increases in CA1 activity after footshock that were not observed after tone termination. Optogenetic silencing of CA1 immediately after footshock impaired subsequent memory. Additionally, footshock increased the number of sharp-wave ripples compared to baseline during conditioning. Therefore, post-shock hippocampal activity likely supports learning by reactivating and linking latent tone and shock representations. These findings highlight an underappreciated function of post-trial hippocampal activity in enabling retroactive temporal associations during new learning, as opposed to persistent maintenance of stimulus representations.
在不同时间发生的绑定事件对于记忆形成至关重要。在痕迹恐惧条件反射中，尽管声音和足部电击之间没有时间重叠，动物仍能将二者联系起来。海马体被认为通过维持对声音的记忆直到电击出现来介导这种学习，然而，缺乏海马体持续声音表征的证据。在这里，我们证明了海马体在痕迹恐惧条件反射中的回顾性作用。整体钙成像显示，足部电击后CA1活性持续增加，而在声音终止后未观察到这种情况。足部电击后立即对CA1进行光遗传学沉默会损害随后的记忆。此外，与条件反射期间的基线相比，足部电击增加了尖波涟漪的数量。因此，电击后海马体活动可能通过重新激活并连接潜在的声音和电击表征来支持学习。这些发现突出了试验后海马体活动在新学习过程中实现追溯性时间关联方面未被充分认识的功能，而不是持续维持刺激表征。
