Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Ave., Toronto, ON M5G 1X8, Canada.
Program in Neurosciences & Mental Health, Hospital for Sick Children, 555 University Ave., Toronto, ON M5G 1X8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Neuron. 2023 Jun 7;111(11):1830-1845.e5. doi: 10.1016/j.neuron.2023.03.007. Epub 2023 Mar 28.
According to the encoding specificity hypothesis, memory is best recalled by retrieval cues that overlap with training cues. Human studies generally support this hypothesis. However, memories are thought to be stored in neuronal ensembles (engrams), and retrieval cues are thought to reactivate neurons in an engram to induce memory recall. Here, we visualized engrams in mice to test whether retrieval cues that overlap with training cues produce maximal memory recall via high engram reactivation (engram encoding specificity hypothesis). Using variations of cued threat conditioning (pairing conditioned stimulus [CS] with footshock), we manipulated encoding and retrieval conditions along multiple domains, including pharmacological state, external sensory cue, and internal optogenetic cue. Maximal engram reactivation and memory recall occurred when retrieval conditions closely matched training conditions. These findings provide a biological basis for the encoding specificity hypothesis and highlight the important interaction between stored information (engram) and cues available at memory retrieval (ecphory).
根据编码特异性假说，记忆通过与训练线索重叠的检索线索被最好地回忆起来。人类研究通常支持这一假说。然而，记忆被认为储存在神经元集合体（记忆痕迹）中，检索线索被认为通过重新激活记忆痕迹中的神经元来诱导记忆回忆。在这里，我们在小鼠中可视化了记忆痕迹，以测试与训练线索重叠的检索线索是否通过高记忆痕迹再激活（记忆痕迹编码特异性假说）产生最大的记忆回忆。使用条件性威胁（将条件刺激与足底电击配对）的变化，我们沿着多个领域操纵了编码和检索条件，包括药理学状态、外部感觉线索和内部光遗传学线索。当检索条件与训练条件非常匹配时，记忆痕迹的最大再激活和记忆回忆发生。这些发现为编码特异性假说提供了生物学基础，并强调了存储信息（记忆痕迹）和记忆检索时可用线索（表象）之间的重要相互作用。
