Program in Neurosciences and Mental Health, Hospital for Sick Children, 555 University Avenue , Toronto, Ontario M5G 1X8, Canada.
Department of Physiology, University of Toronto , Toronto, Ontario M5G 1X8, Canada.
Philos Trans R Soc Lond B Biol Sci. 2024 Jul 29;379(1906):20230227. doi: 10.1098/rstb.2023.0227. Epub 2024 Jun 10.
Memories are thought to be stored within sparse collections of neurons known as engram ensembles. Neurons active during a training episode are allocated to an engram ensemble ('engram neurons'). Memory retrieval is initiated by external sensory or internal cues present at the time of training reactivating engram neurons. Interestingly, optogenetic reactivation of engram ensemble neurons alone in the absence of external sensory cues is sufficient to induce behaviour consistent with memory retrieval in mice. However, there may exist differences between the behaviours induced by natural retrieval cues or artificial engram reactivation. Here, we compared two defensive behaviours (freezing and the syllable structure of ultrasonic vocalizations, USVs) induced by sensory cues present at training (natural memory retrieval) and optogenetic engram ensemble reactivation (artificial memory retrieval) in a threat conditioning paradigm in the same mice. During natural memory recall, we observed a strong positive correlation between freezing levels and distinct USV syllable features (characterized by an unsupervised algorithm, MUPET (Mouse Ultrasonic Profile ExTraction)). Moreover, we observed strikingly similar behavioural profiles in terms of freezing and USV characteristics between natural memory recall and artificial memory recall in the absence of sensory retrieval cues. Although our analysis focused on two behavioural measures of threat memory (freezing and USV characteristics), these results underscore the similarities between threat memory recall triggered naturally and through optogenetic reactivation of engram ensembles. This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
记忆被认为储存在稀疏的神经元集合中，称为记忆痕迹集合。在训练过程中活跃的神经元被分配到一个记忆痕迹集合（“记忆痕迹神经元”）中。记忆检索是由训练时出现的外部感觉或内部线索引发的，这些线索重新激活记忆痕迹神经元。有趣的是，仅通过光遗传学重新激活记忆痕迹集合神经元，而没有外部感觉线索，就足以在小鼠中引发与记忆检索一致的行为。然而，自然检索线索或人工记忆痕迹再激活引发的行为之间可能存在差异。在这里，我们在相同的威胁条件反射范式中比较了两种防御行为（冻结和超声发声的音节结构，USVs），这些行为由训练时出现的感觉线索（自然记忆检索）和光遗传学记忆痕迹集合再激活（人工记忆检索）引起。在自然记忆回忆期间，我们观察到冻结水平与独特的 USV 音节特征之间存在强烈的正相关关系（由无监督算法 MUPET（Mouse Ultrasonic Profile ExTraction）描述）。此外，我们观察到在没有感觉检索线索的情况下，自然记忆回忆和人工记忆回忆之间在冻结和 USV 特征方面具有惊人相似的行为特征。尽管我们的分析集中在威胁记忆的两种行为测量上（冻结和 USV 特征），但这些结果强调了自然触发和通过光遗传学再激活记忆痕迹集合引发的威胁记忆回忆之间的相似性。本文是关于“长时程增强作用：50 年的研究进展”讨论会议的一部分。
