Retroactive interference of object‐in‐context long‐term memory: Role of dorsal hippocampus and medial prefrontal cortex

Abstract

Retroactive interference (RI) is a type of amnesia in which a new learning experience can impair the expression of a previous one. It has been studied in several types of memories for over a century. Here, we aimed to study in the long-term memory (LTM) formation of an object-in-context task, defined as the recognition of a familiar object in a context different to that in which it was previously encountered. We trained rats with two sample trials, each taking place in a different context in association with different objects. Test sessions were performed 24 h later, to evaluate LTM for both object-context pairs using separate groups of trained rats. Furthermore, given the involvement of hippocampus (Hp) and medial prefrontal cortex (mPFC) in several recognition memories, we also analyzed the participation of these structures in the LTM formation of this task by the local infusion of muscimol. Our results show that object-in-context LTM formation is sensitive to RI by a different either familiar or novel object-context pair trial, experienced 1 h later. This interference occurs in a restricted temporal window and works on the LTM consolidation phase, leaving intact short-term memory expression. The second sample trial did not affect the object recognition part of the memory. Besides, muscimol treatment before the second sample trial blocks its object-in-context LTM and restores the first sample trial memory. We hypothesized that LTM-RI amnesia is probably caused by resources or cellular machinery competition in these brain regions when they are engaged in memory formation of the traces. In sum, when two different object-in-context memory traces are being processed, the second trace interferes with the consolidation of the first one requiring mPFC and CA1 dorsal Hp activation.

Ontogeny of object-in-context recognition in the rat

“…Exploration ratios for these are a more conservative measure in our short-term memory test because recognition memory based on recency [29] and recognition memory based on context are not confounded as in Context Orders ABB and BAA. Additionally, consistent with our findings from Experiment 1, it has been demonstrated in the literature that context order is not a significant factor in tests of short-term OiC memory [30]. In the Different group, where rats were tested in a familiar context not experienced during either sample phase, the novel target was designated as the object that would have been novel if the rat was tested in the Sample 1 context.…”

“…To our knowledge, this is the first study to report the ontogeny of object-in-context recognition. Numerous studies have demonstrated the ability of adult rats to perform the OiC task [12, 18, 19, 30, 34-40]; however, the youngest age reported is approximately PD50 [41]. Our observation that OiC task performance emerges by PD17 is similar to the emergence of standard object recognition (OR) [14-17], but not other forms of spatial recognition memory like the object location recognition (OL) task, which emerges between PD17 and PD21 [17], or the 2-object variant of the object-in-place (OiP) task, which emerges between PD24 and 31 [15].…”

“…This is the first study to test the assumption that contextual stimuli drive novelty preference in the OiC task. In a recent study in which long-term OiC memory was examined, contexts were manipulated during the second sample phase [30]; however, this manipulation did not allow the experimenters to identify the strategy by which rats were performing their task. Context has also been manipulated in studies employing the OR task.…”

“…Likewise, the current literature suggests that the OiC task relies on function of the hippocampal system in adult rats [12, 30, 34, 36, 38, 39], with a few exceptions [18, 37]. The disparate findings regarding the role of the hippocampus in OiC memory may reflect variable delays employed by different studies which differentially recruit short-term vs. long-term memory processes, or variation in the degree of spatial processing required for discrimination of the contexts during the task.…”

Determinants of object‐in‐context and object‐place‐context recognition in the developing rat

“…It is unknown whether developing rats can remember object-context associations over longer delays. Therefore, in an additional 24 hr retention group, sample phases were separated by a longer 4 hr delay (Group LD + LTM), as these parameters did not produce interference in a test of long-term OiC memory in the aforementioned study (Martínez et al, 2014). A recent study showed long-term OiC task performance in adult rats and found that memory for object-context associations is subject to retroactive interference when encoding of the multiple associations occurs within a short temporal window (Martínez, Villar, Ballarini, & Viola, 2014).…”