O'Neill Olivia S, George Karley V, Minard Emily P, Winters Boyer D
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, 50 Stone Road E, Guelph, ON N1G 2W1, Canada.
Department of Psychology and Collaborative Neuroscience Program, University of Guelph, 50 Stone Road E, Guelph, ON N1G 2W1, Canada.
Neurobiol Learn Mem. 2025 Jan;217:108017. doi: 10.1016/j.nlm.2024.108017. Epub 2024 Dec 16.
Consolidated long-term memories can undergo strength or content modification via protein synthesis-dependent reconsolidation. This is the process by which a reminder cue initiates reactivation of the memory trace, triggering destabilization. Older and more strongly encoded spatial memories can resist destabilization due to biological boundary conditions. The present study investigated the role of dopamine (DA) at D1 receptors (D1Rs) in object location memory destabilization and overcoming boundary conditions for older ("remote"; tested with a 48-h rather than a 24-h delay between sample and reactivation) memory destabilization. Using male rats in a modified object location task, we found that administering the D1R antagonist SCH23390 (0.1 mg/kg, i.p.) prior to reactivation blocked destabilization of recently encoded memories, as well as novelty-induced destabilization of remote memories. Using remote parameters, systemically administered D1R agonist SKF38393 (5 mg/kg, i.p.) induced destabilization of remote object location memories in the absence of salient novelty. Intra-dorsal hippocampus administration of SCH23390 (2 μg/μL) also blocked destabilization of remote object location memories when a salient novel cue was present. These results are consistent with previous findings implicating DA in memory destabilization as well as demonstrate a role for D1-receptor activation in the destabilization of boundary condition protected-object location memories.
巩固的长期记忆可通过蛋白质合成依赖性再巩固进行强度或内容的修改。这是一个提示线索启动记忆痕迹再激活，引发不稳定的过程。由于生物学边界条件，形成时间较早且编码更强的空间记忆能够抵抗不稳定。本研究调查了多巴胺（DA）在D1受体（D1Rs）上对物体位置记忆不稳定以及克服旧记忆（“远期”；在样本和再激活之间延迟48小时而非24小时进行测试）不稳定的边界条件方面所起的作用。在改良的物体位置任务中使用雄性大鼠，我们发现，在再激活前给予D1R拮抗剂SCH23390（0.1毫克/千克，腹腔注射）可阻止近期编码记忆的不稳定，以及新奇诱导的远期记忆不稳定。采用远期参数，全身给予D1R激动剂SKF38393（5毫克/千克，腹腔注射）在没有显著新奇性的情况下可诱导远期物体位置记忆的不稳定。当存在显著的新奇线索时，背侧海马内注射SCH23390（2微克/微升）也可阻止远期物体位置记忆的不稳定。这些结果与之前将DA与记忆不稳定联系起来的研究结果一致，同时也证明了D1受体激活在边界条件保护的物体位置记忆不稳定中所起的作用。
