Laboratory of Memory Research and Molecular Cognition, Institute for Cell Biology and Neuroscience CONICET and University of Buenos Aires Medical School, Buenos Aires, Argentina.
Department of Medicine, University of British Columbia, Vancouver, BC, Canada.
eNeuro. 2017 Oct 18;4(5). doi: 10.1523/ENEURO.0293-17.2017. eCollection 2017 Sep-Oct.
Successful memory involves not only remembering over time but also keeping memories distinct. The ability to separate similar experiences into distinct memories is a main feature of episodic memory. Discrimination of overlapping representations has been investigated in the dentate gyrus of the hippocampus (DG), but little is known about this process in other regions such as the perirhinal cortex (Prh). We found in male rats that perirhinal brain-derived neurotrophic factor (BDNF) is required for separable storage of overlapping, but not distinct, object representations, which is identical to its role in the DG for spatial representations. Also, activity-regulated cytoskeletal-associated protein (Arc) is required for disambiguation of object memories, as measured by infusion of antisense oligonucleotides. This is the first time Arc has been implicated in the discrimination of objects with overlapping features. Although molecular mechanisms for object memory have been shown previously in Prh, these have been dependent on delay, suggesting a role specifically in memory duration. BDNF and Arc involvement were independent of delay-the same demand for memory persistence was present in all conditions-but only when discrimination of similar objects was required were these mechanisms recruited and necessary. Finally, we show that BDNF and Arc participate in the same pathway during consolidation of overlapping object memories. We provide novel evidence regarding the proteins involved in disambiguation of object memories outside the DG and suggest that, despite the anatomical differences, similar mechanisms underlie this process in the DG and Prh that are engaged depending on the similarity of the stimuli.
成功的记忆不仅涉及随着时间的推移而记忆，还涉及保持记忆的独特性。将相似的经验分离为独特记忆的能力是情景记忆的主要特征。在海马齿状回（DG）中已经研究了重叠表示的辨别，但对于其他区域（如边缘前皮质（Prh））中的此过程知之甚少。我们在雄性大鼠中发现，边缘前皮质脑源性神经营养因子（BDNF）是重叠但不独特的物体表示可分离存储所必需的，这与它在 DG 中对空间表示的作用相同。另外，活性调节细胞骨架相关蛋白（Arc）是区分物体记忆所必需的，如通过反义寡核苷酸的输注来测量。这是 Arc 首次被牵连到具有重叠特征的物体的辨别中。尽管先前已经在 Prh 中显示了物体记忆的分子机制，但这些机制依赖于延迟，表明其在记忆持续时间上具有特定作用。BDNF 和 Arc 的参与与延迟无关-所有条件都存在对记忆持久性的相同需求-但只有在需要区分相似物体时，才会招募这些机制并使其成为必需。最后，我们证明 BDNF 和 Arc 在重叠物体记忆的巩固过程中参与相同的途径。我们提供了有关 DG 以外的物体记忆消除中涉及的蛋白质的新证据，并表明，尽管存在解剖差异，但 DG 和 Prh 中存在类似的机制来参与此过程，具体取决于刺激的相似性。
