Sex and Estrous Cycle in Memory for Sequences of Events in Rats

The ability to remember sequences of events is fundamental to episodic memory. While rodent studies have examined sex and estrous cycle in episodic-like spatial memory tasks, little is known about these biological variables in memory for sequences of events that depend on representations of temporal context. We investigated the role of sex and estrous cycle in rats during all training and testing stages of a cross-species validated sequence memory task (Jayachandran et al., 2019). Rats were trained on a task composed of two sequences, each with four unique odors delivered on opposite ends of a linear track. Training occurred in six successive stages starting with learning to poke in a nose port for ≥1.2s; eventually demonstrating sequence memory by holding their nose in the port for ≥1s for in-sequence odors and <1s for out-of-sequence odors in order to receive a water reward. Performance was analyzed across sex and estrous cycle (proestrus, estrus, metestrus, and diestrus), the latter being determined by the cellular composition of a daily vaginal lavage. We found no evidence of sex differences in asymptotic sequence memory performance, similar to published data in humans performing the analogous task (Reeders et al., 2021). Likewise, we found no differences in performance across the estrous cycle. One minor difference was that female rats tended to have slightly longer poke times, while males had slightly more short poke times but this did not affect their decisions. These results suggest sex and estrous cycle are not major factors in sequence memory capacities.

Recursive Processing of Nested Structures in Monkeys? Two alternative accounts

Ferrigno et al. [2020] introduced an ingenious task to investigate recursion in human and non-human primates. American adults, Tsimane adults, and 3-5 year-old children successfully performed the task. Macaque monkeys required additional training, but two out of three eventually showed good generalization and scored above many Tsimane and child participants. Moreover, when tested on sequences composed of new bracket signs, the monkeys still showed good performance. The authors thus concluded that recursive nesting is not unique to humans. Here, we dispute the claim by showing that at least two alternative interpretations remain tenable. We first examine this conclusion in light of recent findings from modern artificial recurrent neural networks (RNNs), regarding how these networks encode sequences. We show that although RNNs, like monkeys, succeed on demanding generalization tasks as in Ferrigno et al., the underlying neural mechanisms are not recursive. Moreover, we show that when the networks are tested on sequences with deeper center-embedded structures compared to training, the networks fail to generalize. We then discuss an additional interpretation of the results in light of a simple model of sequence memory.

Contextual prediction errors reorganize naturalistic episodic memories in time

Episodic memories are contextual experiences ordered in time. This is underpinned by associative binding between events within the same contexts. The role of prediction errors in declarative memory is well established but has not been investigated in the time dimension of complex episodic memories. Here we combine these two properties of episodic memory, extend them into the temporal domain and demonstrate that prediction errors in different naturalistic contexts lead to changes in the temporal ordering of event structures in them. The wrongly predicted older sequences were weakened despite their reactivation. Interestingly the newly encoded sequences with prediction errors, seen once, showed accuracy as high as control sequences which were viewed repeatedly without change. Drift–diffusion modelling revealed a lower decision threshold for the newer sequences than older sequences, reflected by their faster recall. Moreover, participants’ adjustments to their decision threshold significantly correlated with their relative speed of sequence memory recall. These results suggest a temporally distinct and adaptive role for prediction errors in learning and reorganizing episodic temporal sequences.

The effect of stress on memory for temporal context: an exploratory study

ABSTRACTTrauma memories can appear dissociated from their original temporal context, and are often relived as they occur in the here-and-now. Potentially these temporal distortions already occur during encoding of the aversive experience as a consequence of stress. Here, 86 participants were subjected to either a stress or control induction, after which they learned the temporal structure of four virtual days. In these virtual days, time was scaled and participants could use clock cues to construe the passage of time within a day. We examined whether stress causes a shift in the learning strategy from one based on virtual time to one based on event sequence. Our results do not show a discernible impact of stress on memory for temporal context, in terms of both sequence memory and more fine-grained representations of time. The stress groups showed more extreme performance trajectories, either good or poor, across all measures. However, as time estimations were overall quite poor it is unclear to what extent this reflected a true strategy shift. Future avenues of research that can build on these findings are discussed.

Contextual Prediction Errors Reorganize Naturalistic Episodic Memories in Time

Episodic memories are contextual experiences ordered in time. This is underpinned by associative binding between events within the same contexts. The role of prediction errors in declarative memory is well established but has not been investigated in the time dimension of complex episodic memories. Here we combine these two properties of episodic memory, extend them into the temporal domain and demonstrate that prediction errors in different naturalistic contexts lead to changes in the temporal ordering of event structures in them. The wrongly predicted older sequences were weakened despite reactivating them after. Interestingly, the newly encoded sequences with prediction errors, seen once, showed as high accuracy as control sequences which were viewed repeatedly without change. Drift-diffusion modelling revealed a lower decision threshold for the newer sequences compared to older sequences, reflected by their faster recall. Moreover participants’ adjustments to their decision threshold could significantly predict their relative speed of sequence memory recall. This suggests a temporally distinct and adaptive role for prediction errors in learning and reorganizing episodic sequences.

Dissociated neural representations of content and ordinal structure in auditory sequence memory

When retaining a sequence of auditory tones in working memory (WM), two forms of information – frequency (content) and ordinal position (structure) – have to be maintained in the brain. Here, we employed a time-resolved multivariate decoding analysis on content and structure information separately to examine their neural representations in human auditory WM. We demonstrate that content and structure are stored in a dissociated manner and show distinct characteristics. First, each tone is associated with two separate codes in parallel, characterizing its frequency and ordinal position, respectively. Second, during retention, a structural retrocue reactivates structure but not content, whereas a following white noise triggers content but not structure. Third, structure representation remains unchanged whereas content undergoes a transformation throughout memory progress. Finally, content reactivations during retention correlate with WM behavior. Overall, our results support a factorized content-structure representation in auditory WM, which might help efficient memory formation and storage by generalizing stable structure to new auditory inputs.

Sequence Memory in the Hippocampal–Entorhinal Region

Episodic memories are constructed from sequences of events. When recalling such a memory, we not only recall individual events, but we also retrieve information about how the sequence of events unfolded. Here, we focus on the role of the hippocampal–entorhinal region in processing and remembering sequences of events, which are thought to be stored in relational networks. We summarize evidence that temporal relations are a central organizational principle for memories in the hippocampus. Importantly, we incorporate novel insights from recent studies about the role of the adjacent entorhinal cortex in sequence memory. In rodents, the lateral entorhinal subregion carries temporal information during ongoing behavior. The human homologue is recruited during memory recall where its representations reflect the temporal relationships between events encountered in a sequence. We further introduce the idea that the hippocampal–entorhinal region might enable temporal scaling of sequence representations. Flexible changes of sequence progression speed could underlie the traversal of episodic memories and mental simulations at different paces. In conclusion, we describe how the entorhinal cortex and hippocampus contribute to remembering event sequences—a core component of episodic memory.