Although the hippocampus has been implicated in both the temporal organization of memories and association of scene elements, some theoretical accounts posit that the role of the hippocampus in episodic memory is largely atemporal. In this study, we set out to explore this discrepancy by identifying hippocampal activity patterns related to scene construction while participants performed a temporal order memory task. Participants in the fMRI scanner were shown a sequence of photographs, each consisting of a central object and a contextual background scene. On each retrieval trial, participants were shown a pair of the original photographs (FULL), objects from the scenes without the background (OBJ), or background contexts without the main foreground object (BACK). In the temporal order judgment (TOJ) task, participants judged the temporal order of the pair of scenes; in the Viewing trials, two identical scenes were shown without any task. First, we found that the anterior hippocampus-particularly the CA1 and subiculum-showed similar patterns of activation between the BACK and OBJ conditions, suggesting that scene construction occurred spontaneously during both TOJ and Viewing. Furthermore, neural markers of scene construction in the anterior hippocampus did not apply to incorrect trials, showing that successful temporal memory retrieval was functionally linked to scene construction. In the cortex, time-processing areas, such as the supplementary motor area and the precuneus, and scene-processing areas, such as the parahippocampal cortex, were activated and functionally connected with the hippocampus. Together, these results support the view that the hippocampus is concurrently involved in scene construction and temporal organization of memory and propose a model of hippocampal episodic memory that takes both processes into account.

Our actions shape our everyday experience: what we experience, how we perceive, and remember it are deeply affected by how we interact with the world. Performing an action to deliver a stimulus engages neurophysiological processes which are reflected in the modulation of sensory and pupil responses. We hypothesized that these processes shape memory encoding, parsing the experience by grouping self- and externally generated stimuli into differentiated events. Participants encoded sound sequences, in which either the first or last few sounds were self-generated and the rest externally generated. We tested recall of the sequential order of sounds that had originated from the same (within event) or different sources (across events). Memory performance was not higher for within-event sounds, suggesting that actions did not structure the memory representation. However, during encoding, we observed the expected electrophysiological response attenuation for self-generated sounds, together with increased pupil dilation triggered by actions. Moreover, at the boundary between events, physiological responses to the first sound from the new source were influenced by the direction of the source switch. Our results suggest that introducing actions creates a stronger contextual shift than removing them, even though actions do not directly contribute to memory performance. This study contributes to our understanding of how interacting with sensory input shapes experiences by exploring the relationships between action effects on sensory responses, pupil dilation, and memory encoding. Importantly, it challenges the notion of a meaningful contribution from low-level neurophysiological mechanisms associated with action execution in the modulation of the self-generation effect.

The temporal component of episodic memory has been recognized as a sensitive behavioral marker in early stage of Alzheimer\'s disease (AD) patients. However, parallel studies in AD animals are currently lacking, and the underlying neural circuit mechanisms remain poorly understood. Using a novel AppNL-G-F knock-in (APP-KI) rat model, the developmental changes of temporal order memory (TOM) and the relationship with medial prefrontal cortex and perirhinal cortex (mPFC-PRH) circuit were determined through in vivo electrophysiology and microimaging technique. We observed a deficit in TOM performance during the object temporal order memory task (OTOMT) in APP-KI rats at 6 month old, which was not evident at 3 or 4 months of age. Alongside behavioral changes, we identified a gradually extensive and aggravated regional activation and functional alterations in the mPFC and PRH during the performance of OTOMT, which occurred prior to the onset of TOM deficits. Moreover, coherence analysis showed that the functional connectivity between the mPFC and PRH could predict the extent of future behavioral performance. Further analysis revealed that the aberrant mPFC-PRH interaction mainly attributed to the progressive deterioration of synaptic transmission, information flow and network coordination from mPFC to PRH, suggesting the mPFC dysfunction maybe the key area of origin underlying the early changes of TOM. These findings identify a pivotal role of the mPFC-PRH circuit in mediating the TOM deficits in the early stage of AD, which holds promising clinical translational value and offers potential early biological markers for predicting AD memory progression.

Temporal order memory is impaired in autism spectrum disorder (ASD) and schizophrenia (SCZ). These disorders, more prevalent in males, result in abnormal dendritic spine pruning during adolescence in layer 3 (L3) medial prefrontal cortex (mPFC), yielding either too many (ASD) or too few (SCZ) spines. Here we tested whether altering spine density in neural circuits including the mPFC could be associated with impaired temporal order memory in male mice. We have shown that α4βδ GABAA receptors (GABARs) emerge at puberty on spines of L5 prelimbic mPFC (PL) where they trigger pruning. We show here that α4βδ receptors also increase at puberty in L3 PL (P < 0.0001) and used these receptors as a target to manipulate spine density here. Pubertal injection (14 d) of the GABA agonist gaboxadol, at a dose (3 mg/kg) selective for α4βδ, reduced L3 spine density by half (P < 0.0001), while α4 knock-out increased spine density ∼ 40 % (P < 0.0001), mimicking spine densities in SCZ and ASD, respectively. In both cases, performance on the mPFC-dependent temporal order recognition task was impaired, resulting in decreases in the discrimination ratio which assesses preference for the novel object: -0.39 ± 0.15, gaboxadol versus 0.52 ± 0.09, vehicle; P = 0.0002; -0.048 ± 0.10, α4 KO versus 0.49 ± 0.04, wild-type; P < 0.0001. In contrast, the number of approaches was unaltered, reflecting unchanged locomotion. These data suggest that altering α4βδ GABAR expression/activity alters spine density in L3 mPFC and impairs temporal order memory to mimic changes in ASD and SCZ. These findings may provide insight into these disorders.

Our daily lives unfold continuously, yet our memories are organised into distinct events, situated in a specific context of space and time, and chunked when this context changes (at event boundaries). Previous research showed that this process, termed event segmentation, enhances object-context binding but impairs temporal order memory. Physiologically, peaks in pupil dilation index event segmentation, similar to emotion-induced bursts of autonomic arousal. Emotional arousal also modulates object-context binding and temporal order memory. Yet, these two critical factors have not been systematically studied together. To address this gap, we ran a behavioural experiment using a paradigm validated to study event segmentation and extended it with emotion manipulation. During encoding, we sequentially presented greyscale objects embedded in coloured frames (colour changes defining events), with a neutral or aversive sound. During retrieval, we tested participants\' memory of temporal order memory and object-colour binding. We found opposite effects of emotion and event segmentation on episodic memory. While event segmentation enhanced object-context binding, emotion impaired it. On the contrary, event segmentation impaired temporal order memory, but emotion enhanced it. These findings increase our understanding of episodic memory organisation in laboratory settings, and potentially in real life with perceptual changes and emotion fluctuations constantly interacting.

In humans, cocaine abuse during adolescence poses a significant risk for developing cognitive deficits later in life. Among the regions responsible for cognitive processes, the medial prefrontal cortex (mPFC) modulates temporal order information via mechanisms involving the mammalian-target of rapamycin (mTOR)-mediated pathway and protein synthesis regulation. Accordingly, our goal was to study the effect of repeated cocaine exposure during both adolescence and adulthood on temporal memory by studying the mTOR pathway in the mPFC. Adolescent or adult rats underwent repeated cocaine injections for 15 days and, after two weeks of withdrawal, engaged in the temporal order object recognition (TOOR) test. We found that repeated cocaine exposure during adolescence impaired TOOR performance, while control or adult-treated animals showed no impairments. Moreover, activation of the mTOR-S6-eEF2 pathway following the TOOR test was diminished only in the adolescent cocaine-treated group. Notably, inhibition of the mTOR-mediated pathway by rapamycin injection impaired TOOR performance in naïve adolescent and adult animals, revealing this pathway to be a critical component in regulating recency memory. Our data indicate that withdrawal from cocaine exposure impairs recency memory via the dysregulation of protein translation mechanisms, but only when cocaine is administered during adolescence.

Temporal order memory refers to the ability to remember the order of occurrence of items across time. It is a critical feature of episodic memory that is often tested in rodents using spontaneous object recognition paradigms. However, impact of aging over performances of temporal order memory decline is barely known. Herein, we characterized here the effect of normal aging on the temporal order memory performances in NMRI mice between 3 and 19months of age, with an inter-session interval of 24h.We found that temporal order memory was impaired as soon as7 months of age. These results provide strong evidence that temporal order memory is particularly vulnerable to the deleterious effect of normal aging.

Meaningful changes in context create \"event boundaries\", segmenting continuous experience into distinct episodes in memory. A foundational finding in this literature is that event boundaries impair memory for the temporal order of stimuli spanning a boundary compared to equally spaced stimuli within an event. This seems surprising in light of intuitions about memory in everyday life, where the order of within-event experiences (did I have coffee before the first bite of bagel?) often seems more difficult to recall than the order of events per se (did I have breakfast or do the dishes first?). Here, we aimed to resolve this discrepancy by manipulating whether stimuli carried information about their encoding context during retrieval, as they often do in everyday life (e.g., bagel-breakfast). In Experiments 1 and 2, we show that stimuli inherently associated with a unique encoding context produce a \"flipped\" order memory effect, whereby temporal memory was superior for cross-boundary than within-event item pairs. In Experiments 3 and 4, we added context information at retrieval to a standard laboratory event memory protocol where stimuli were encoded in the presence of arbitrary context cues (colored frames). We found that whether temporal order memory for cross-boundary stimuli was enhanced or impaired relative to within-event items depended on whether the context was present or absent during the memory test. Taken together, we demonstrate that the effect of event boundaries on temporal memory is malleable, and determined by the availability of context information at retrieval.

Item recognition and temporal order memory follow different developmental trajectories during middle childhood, with item recognition performance stabilizing and temporal order memory performance continuing to improve. We investigated the potential unique role of individual executive functions on item recognition and temporal order memory during this critical development period. Our results replicate and expand on previous findings, suggesting that executive functions, specifically inhibitory control and working memory, may be more crucial for successful temporal order memory than for item recognition during middle childhood.

The hippocampus plays an important role in representing spatial locations and sequences and in transforming representations. How these representational structures and operations support memory for the temporal order of random items is still poorly understood. We addressed this question by leveraging the method of loci, a powerful mnemonic strategy for temporal order memory that particularly recruits hippocampus-dependent computations of spatial locations and associations. Applying representational similarity analysis to functional magnetic resonance imaging activation patterns revealed that hippocampal subfields contained representations of multiple features of sequence structure, including spatial locations, location distance, and sequence boundaries, as well as episodic-like temporal context. Critically, the hippocampal CA1 exhibited spatial transformation of representational patterns, showing lower pattern similarity for items in same locations than closely matched different locations during retrieval, whereas the CA23DG exhibited sequential transformation of representational patterns, showing lower pattern similarity for items in near locations than in far locations during encoding. These transformations enabled the encoding of multiple items in the same location and disambiguation of adjacent items. Our results suggest that the hippocampus can flexibly reconfigure multiplexed event structure representations to support accurate temporal order memory.