Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario, Canada.
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, Ontario, Canada.
Neurobiol Learn Mem. 2022 Nov;195:107686. doi: 10.1016/j.nlm.2022.107686. Epub 2022 Sep 26.
The content of long-term memory is neither fixed nor permanent. Reminder cues can destabilize consolidated memories, rendering them amenable to change before being reconsolidated. However, not all memories destabilize following reactivation. Characteristics of a memory, such as its age or strength, impose boundaries on destabilization. Previously, we demonstrated that presentation of salient novel information at the time of reactivation can readily destabilize resistant object memories in rats and this form of novelty-induced destabilization is dependent upon acetylcholine (ACh) activity at muscarinic receptors (mAChRs). In the present study, we sought to determine if this same mechanism for initiating destabilization of resistant object memories is present in mice and further expand our understanding of the mechanisms through which ACh modulates object memory destabilization by investigating the role of nicotinic receptors (nAChRs). We provide evidence that in mice mAChRs are necessary for destabilizing object memories that are readily destabilized and those that are resistant to destabilization. Conversely, nAChRs were found to be necessary only when memories are readily destabilized. We then investigated the role of both receptors in the reconsolidation of destabilized object memory traces and determined that nAChRs, but not mAChRs, are necessary for object memory reconsolidation. Together, these results suggest that nAChRs may play a more selective role in the re-storage of object memories following destabilization and that ACh acts through mAChRs to act as an override signal to initiate destabilization of resistant object memories following reactivation with novelty. These findings expand our current understanding of the role of ACh in the dynamic storage of long-term memory.
长期记忆的内容既不稳定也不固定。提示线索可以使已巩固的记忆不稳定，从而在重新巩固之前使其易于改变。然而，并非所有记忆在重新激活后都会不稳定。记忆的特征，如其年龄或强度，对不稳定施加限制。以前，我们证明在重新激活时呈现突出的新信息可以轻易地使大鼠中具有抗性的物体记忆不稳定，这种形式的新奇诱导的不稳定性依赖于毒蕈碱型乙酰胆碱受体（mAChRs）上的乙酰胆碱（ACh）活性。在本研究中，我们试图确定在小鼠中是否存在这种引发抗性物体记忆不稳定的相同机制，并通过研究 ACh 调节物体记忆不稳定的机制进一步扩展我们的理解，即通过调查烟碱型乙酰胆碱受体（nAChRs）的作用。我们提供的证据表明，在小鼠中 mAChRs 对于容易不稳定和抵抗不稳定的物体记忆的不稳定是必需的。相反，只有当记忆容易不稳定时，nAChRs 才被发现是必需的。然后，我们研究了这两种受体在不稳定的物体记忆痕迹的再巩固中的作用，并确定 nAChRs 但不是 mAChRs 对于物体记忆的再巩固是必需的。这些结果表明，nAChRs 可能在不稳定后重新存储物体记忆方面发挥更具选择性的作用，并且 ACh 通过 mAChRs 作为覆盖信号发挥作用，以在重新激活时启动具有抗性的物体记忆的不稳定与新奇。这些发现扩展了我们对 ACh 在长期记忆动态存储中的作用的现有理解。
