Learning & Memory

Stored memories are useless unless they are available for retrieval. Thus, investigating different ways to modulate retrieval is crucial. Novelty has been extensively studied as a modulator of memory. In this study, we investigated whether exposure to a novel event, an innovative neuroscience lesson, can enhance memory retrieval and divergent thinking in high school students. Across three experiments, we assessed the timing and mechanisms underlying these effects. In experiment 1, we found that memory retrieval was enhanced when the novel lesson occurred immediately before a memory test, but not when it was presented one hour earlier. In experiment 2, we found that the same immediate novelty exposure improved divergent thinking performance. Finally, in experiment 3, we explored potential shared mechanisms using a competition protocol and revealed that novelty improved divergent thinking regardless of its timing relative to memory retrieval. However, memory retrieval benefited only when tested immediately before the divergent thinking task. These results suggest that novelty boosts both memory retrieval and divergent thinking, but through partially distinct mechanisms. Our findings demonstrate that a simple, real-world classroom intervention can effectively enhance key cognitive functions in students. Significance StatementStored memories are only valuable if they can be retrieved, and memory retrieval plays a key role in creative thinking. Here, we tested whether a simple, novel event, a neuroscience lesson, could enhance memory retrieval and creative thinking in a real-world classroom setting. We found that novelty improved both memory retrieval and divergent thinking, an aspect of creative thinking, when presented immediately before the task. Finally, we revealed a non-reciprocal competition effect between memory retrieval and divergent thinking. These findings highlight a practical, low-cost intervention to boost key cognitive functions in students, demonstrating that brief, well-timed novel experiences can support both learning and creative thinking in educational environments.

The midsession reversal (MSR) task is frequently used to study behavioral flexibility and decision strategies in animals. In a typical version of the task, subjects complete 80 trials in which they choose between two simultaneously presented stimuli, S1 and S2. During the first 40 trials, responses to S1 are reinforced, whereas responses to S2 are not. The contingencies then reverse without warning: From trial 41 to 80, only responses to S2 are reinforced. In birds, performance in this task is often characterized by anticipatory and perseverative errors around the reversal point, suggesting a reliance on elapsed time since the session began. In contrast, rats tested in operant conditioning chambers typically show near-optimal performance with few errors, a pattern often interpreted as evidence that rats rely primarily on local reinforcement cues rather than temporal information. The present study investigated whether rats exclusively rely on local cues in the MSR task or whether temporal information also contributes to the decision process. Two groups of rats were trained with different intertrial intervals (ITIs; 5 s or 10 s) while the reversal point remained fixed at Trial 41. During acquisition, both groups diplayed similar learning rates and near-optimal steady-state performance with minimal anticipatory or perseverative errors. However, when the ITI was manipulated in probe sessions, systematic shifts in switching behavior emerged. Rats adjusted their choices according to the temporal midpoint experienced during training rather than the nominal trial number of the reversal. These results suggest that rats rely on a mixed strategy that integrates local reinforcement cues with global timing information. Temporal control may therefore be present even when it is not expressed during standard training conditions.

Spatial memory is crucial for navigation and adapting to changing environmental conditions. Known neurophysiological mechanisms of spatial memory center on the importance of hippocampal activity and its spatial tuning. Yet, the behavioral strategies that support adaptive spatial encoding remain poorly understood. We have shown that dorsal hippocampal activity during rearing is necessary for spatial working memory, highlighting a role of information seeking behaviors for spatial memory encoding. Similarly, spatial tuning by dorsal hippocampal neurons is substantially updated during another information seeking behavior: attentive head scanning. However, the functional relationship between these behaviors is unknown. Here, to assess the relevance of environmental context for the expression of these behaviors, we quantified rearing and head scanning in a radial-arm-maze spatial working memory task while manipulating the height of the maze walls. Our goal was to test whether the stereotyped patterns of rearing that rats generate with tall walls are replaced with attentive head scanning when the walls are short enough to reach the top without rearing. We found that rats reared significantly less often when the walls were shortened and, instead, exhibited frequent attentive head scanning. The head scanning was done when and where the rats had previously exhibited stereotyped rearing. These results support the hypothesis that rearing and head scanning are functionally related behaviors. Future work should test two key inferences: 1) Head scanning is a critical epoch of spatial memory encoding, and 2) Spatial tuning by hippocampal neurons is updated during rearing. Significance statementSpatial memory is a core cognitive function, essential for healthy independent living. Though the hippocampus is critical for spatial memory, it remains unclear when and how. Separate prior studies link rearing and lateral head scanning to key periods of hippocampal processing, suggesting both behaviors support sensory information gathering for updating cognitive maps. However, their relationship is unresolved. Here, we test whether these behaviors are functionally interchangeable, with environmental structure determining expression. In a radial-arm maze, rats reared frequently with 21 cm walls but showed reduced rearing when walls were shortened to 4.6 cm, instead increasing head scanning at similar locations. These findings suggest rearing and head scanning share underlying motivations and provide a basis for comparing hippocampal activity during exploration.

Traumatic stress can cause long-lasting changes in cognition and affect, sometimes leading to diagnoses such as post-traumatic stress disorder (PTSD). The stress-enhanced fear learning (SEFL) model recapitulates understudied components of PTSD, such as stress-induced sensitization of fear learning. The SEFL procedure entails exposing mice to footshock stress followed later by fear conditioning in a different context. When tested later for recall of fear conditioning, previously stressed mice exhibit enhanced freezing compared to non-stressed controls. Studies have shown that dorsal and ventral dentate gyrus (DG) generates neural ensemble representations of contextual fear, such that fear recall involves reactivation of a sparse set of "engram cells" that were active during fear memory acquisition. How stress affects these hippocampal ensemble representations is unknown. We used SEFL and activity-dependent neuronal tagging with FosTRAP2 mice to investigate effects of stress on fear memory ensembles in rostral and caudal hippocampal DG. FosTRAP2/Ai6 mice received footshock stress or equivalent context exposure without shock in Context A on day 1. Five days later, mice received 1-shock conditioning in Context B and immediately received an injection of 4-OHT (55mg/kg) to tag fear acquisition neurons with the zsGreen reporter. One day later, mice were tested for fear recall in Context B and were perfused 90 minutes after testing. Confirming prior studies, prior stress potentiated 1-shock conditioning in Context B, with stressed mice displaying higher freezing in the Context B test session than non-stressed mice. At the level of neural activity, results showed stress had no effect on the number of zsGreen+ fear ensemble cells or the number of cfos+ recall-activated cells in rostral or caudal DG. However, stress increased reactivation (percentage of zsGreen+ cells expressing cfos) in the caudal but not rostral DG. The results suggest stress potentiates later fear learning by enhancing fear representations in caudal hippocampus, a region of the hippocampus specialized for integrating emotional and motivational valence into memory.

Saccades made during memory maintenance prioritize memory for the saccade target, but it is unclear if this benefit is specific to a location or extends across memorized objects. In three experiments, we examined whether saccadic selection spreads to other locations within the same object. In Experiment 1, we asked observers to remember three oriented Gabors presented either within contour-defined objects or without object structure. A subsequent movement cue prompted observers to move their eyes to the indicated location. We then probed memory for stimuli at locations equidistant from the saccade target, in either the same or a different object. Memory was best for stimuli at locations congruent with the saccade target, and consistently weaker for other stimuli presented in the same or a different object than the saccade target. In Experiment 2, we created more complex objects by adding more object features to the stimulus. Again, memory performance was best for stimuli congruent with the saccade target location, whereas memory in incongruent trials was worse and similar for stimuli in the same and different object as the saccade target. In Experiment 3, we tested if saccadic selection is present and propagates within the object in a change detection task. Again, memory performance (i.e., change detection) was best at the saccade target location. However, this memory benefit also spread to other locations within the same object. Our results imply that saccadic selection in visual working memory is primarily space-based but can also spread towards locations within the object where a saccade was directed.

Memory generalization allows individuals to extract and apply information from prior experiences to novel situations, supporting flexible learning and efficient decision-making. Theoretical models suggest that sleep should facilitate generalization, yet the literature examining its role in promoting generalization is mixed. We recruited 137 participants via Prolific to complete an image-location memory task over two sessions spaced 12 hours apart. Participants were randomly assigned to the Wake group (learning in the morning) or the Sleep group (learning in the evening). In Session 1, participants learned the location of stimuli on the screen and were tested on their memory five minutes later. Twelve hours later, in Session 2, they were tested on their memory again. Stimuli consisted of 160 images from eight semantic categories and were strategically positioned on-screen to test the effects of generalization on retrieval (i.e., category-based memory distortions and biases). After the delay, retrieval was less accurate and demonstrated more generalization. However, these effects were mostly independent of Group, with some evidence for enhanced generalization following a period of wakefulness over sleep. Generalization was also driven by time of day, with more generalization in the evening relative to the morning. Taken together, our results, based on a large online sample, do not support a role for sleep in promoting memory generalization. Significance StatementBehavior is often guided by memories of previous experiences. However, for behavior to be adaptive and flexible (e.g., when encountering never-before-seen stimuli), regularities about the world must be extracted from these memories. This process, termed memory generalization, has been hypothesized to rely on sleep. We used a large online sample to test sleeps role in generalization and found no support for this hypothesis. Our results suggest that sleep and wakefulness contribute to generalization equally, with the latter potentially having a larger contribution.

Object-based tasks are widely used in rodent behavioral research, yet object selection remains largely unsystematic. We present a paired-object validation protocol in which objects differ along one researcher-defined feature, allowing assessment of whether that feature is salient to the animal. Using six object pairs varying in height, color, shape, or aperture presence, we tested two wild-caught mice species with contrasting ecologies. Wood mice (Sylvaemus uralensis) and striped field mice (Apodemus agrarius) showed equal preference for both objects in most pairs, indicating that color, apertures, and apex shape differences are not salient under the tested conditions and can be used interchangeably in object recognition tasks. Height, however, produced ecology-predicted responses: arboreal wood mice avoided the shortest object while open-habitat striped field mice did not. These results demonstrate that the protocol successfully detects feature salience when present and that ecological background predicts which features matter. Summary StatementA systematic paired-object protocol reveals that most researcher-defined features (color, holes, shape) do not affect rodent exploration, but height preferences emerge in ecology-predicted patterns, demonstrating that feature salience is species-specific.

We readily detect structure in our environments, which in turn guides future learning. Disentangling this structure from the superficial features of a specific learning environment provides an especially strong basis for future generalization, but it remains unclear when and how this kind of abstraction occurs. Memory reactivation during sleep has been hypothesized to support such abstraction, but this has yet to be directly tested. Here we examined this hypothesis by teaching participants novel categories in which patterns of feature covariation were governed by different graph structures. Participants then learned a new category, defined by entirely different features, whose structure was either congruent or incongruent with a previously learned category. If structural knowledge is abstracted away from superficial features, it should facilitate transfer when structures are congruent. In Experiment 1, when two categories were learned in immediate succession, participants showed no transfer benefit, suggesting that structure understanding remained tied to the original features. In Experiment 2, we tested whether offline processing promotes abstraction. Participants either remained awake between learning phases spaced 3 hours apart, or took a nap during which a previously learned category was reactivated using targeted memory reactivation (TMR). Transfer benefits emerged only when the reactivated and target categories shared the same structure, and these benefits increased with the number of cues presented during slow-wave sleep. These findings provide the first direct evidence that memory reactivation during sleep promotes the abstraction of structure, enabling knowledge to transfer across learning episodes with no overlap in features.

Interval timing (IT) is the ability to time events in the range from seconds to a few minutes, allowing animals to organize behavior in time at short durations. IT relies on two cognitive functions: 1) Measuring the passage of time; 2) Storing and retrieving temporal memories in a context appropriate manner. The hippocampus (HC) and medial prefrontal cortex (mPFC) have been shown critical to the accuracy and precision of time-contingent instrumental responses in IT. The anatomy supporting mPFC-HC interactions, required for memory encoding and retrieval, include projections from HC to mPFC, and indirect bidirectional connections through the ventral midline thalamus (VMT), most notably reuniens. Here, we explored VMTs role in retrieving fixed-interval (FI) temporal memories. Rats were trained on a 5s FI signaled by an auditory cue and demonstrated temporal memory by poking predominantly at the time of the expected reward. Timing responses on individual trials were classified into on-time, early, and random response. Across sessions, random response trials decreased following training. Next, we switched training to longer intervals (20s or 80s; daily sessions for weeks). To probe the role of the VMT in temporal memory retrieval, we infused the GABAA-agonist muscimol, or saline, before training sessions. Results show that VMT muscimol infusions decreased timing precision. Also, at both intervals, the number of on-time response trials decreased, and the number of random response trials significantly increased. The number of early response trials had no significant change at 20s, and significantly decreased at 80s. Overall, our results suggest that the VMT is critical for precise retrieval of temporal memories. We also describe per-trial response patterns with characteristics consistent across all trained intervals, suggesting multiple behavioral strategies at play during interval timing.

Reward learning can bias attentional selection, but whether spatially biased reinforcement produces durable, context-general changes in spatial priority over days, and what neurophysiological signals track such learning, remains uncertain. We combined electroencephalography (EEG) and pupillometry with a multi-session spatial reward-learning paradigm (Chelazzi et al., 2014) in which targets could appear at eight locations and reward probability was systematically biased across locations during two days of training. A separate baseline/test visual detection task was administered before training and again four days after training to assess delayed transfer under cross-target competition. Training produced strong reward signals across measures. Feedback-locked ERPs (FRN and P300) differentiated outcome valence and reward magnitude and varied systematically with time-on-task, while pupil dilation was larger following high- than low-reward feedback and overall task-evoked responses decreased across blocks. Reward history also modulated stimulus-locked target processing: targets at high- versus low-reward locations differed reliably across N1/N2 and a late positivity, indicating multi-stage value-dependent influences on visual processing during active learning. In contrast, transfer was weak in both behavior and ERPs: behavioral indices did not show a reliable advantage for highly rewarded locations at delayed test, and neural evidence for persistence was limited to an N2 modulation in the most diagnostic high-versus-low comparison, which should be interpreted cautiously given low trial counts. Accordingly, we did not replicate the robust long-term spatial priority effect reported in the original study. Together, these findings reveal strong reward-learning signals but weak cross-task transfer, suggesting limits on how readily spatial reward learning consolidates into persistent, task-general spatial priority-map plasticity across contexts.

Brainstem arousal systems including the locus coeruleus noradrenaline system, re-spond transiently to behaviorally relevant events. Locus coeruleus activity also drives dilations of the pupil, which are often observed during cognitive tasks. The strength of pupil responses during encoding of stimulus material predicts the success of its later retrieval, which might reflect the impact of noradrenaline on synaptic plasticity and memory formation. The pupil also dilates in response to task-irrelevant sounds, which could therefore serve as a valuable tool for investigating causal effects of phasic, pupil-linked arousal on cognition. Here, we evaluated whether task-irrelevant white noise sounds affect memory formation and memory-based decisions. These sounds were played before, during or after the presentation of memoranda (images or spoken words). Memory success was measured in recognition and free recall tasks the day after. Trial-to-trial variations in the amplitude of pupil dilations during word encoding without task-irrelevant sounds predicted memory success. Task-irrelevant white-noise sounds also robustly dilated the pupil but did not improve memory formation for the words or the images. We conclude that pupil-linked arousal processes triggered by task-irrelevant sounds differ from those recruited endogenously during memory for-mation, for example in states of increased emotionality or attention.

Cognitive flexibility, switching behaviour responses to changing task demands, is classically attributed to the prefrontal cortex. Yet thalamocortical circuits involving the mediodorsal thalamus (MD) and thalamic nucleus reuniens (Re) are dysfunctional across a range of neurological conditions with cognitive flexibility deficits. Interventions involving thalamocortical interactions may offer therapeutic benefits. Here we examined the effects of MD or Re bilateral glutamatergic neurotoxic damage in rats on cognitive flexibility using the attentional set-shifting task. Rats must attend to a sensory dimension that reliably predicts reward (intradimensional shift, ID) followed by a shift in attention to a previously irrelevant sensory dimension when contingencies change (extradimensional shift, ED). We found MD rats required more trials to criterion in the ED, while Re rats showed significant impairments on the first of three ID subtasks (ID1) only. Both MD and Re rats required more trials to criterion to complete each subtask than Sham controls. Intraperitoneal noradrenaline (atipamezole 1mg/kg), given 30 minutes prior to the task reduced trials to criterion across all rats, improving cognitive flexibility even after thalamic damage. These findings demonstrate the influence MD and Re contribute to cognitive flexibility and support noradrenergic regulation of thalamocortical circuits as potential therapeutic targets for cognitive flexibility dysfunction.

Relapse-prevention strategies aimed at reducing relapse following abstinence, primarily focus on reducing cravings that lead to drug-seeking triggered by stress, drug-related cues, or re-exposure to the drug. Because addictive drugs form persistent associative contextual memories, we investigated how reactivation of cocaine-related hippocampal memories influences subsequent drug-seeking. Here, we tagged dorsal dentate gyrus (dDG) memory ensembles involved in encoding either a first or fourth cocaine exposure (15mg/kg, i.p) in male and female c57BL/6 mice using a TetTag approach. Mice underwent cocaine conditioned place preference (CPP), extinction, and reinstatement. We assessed whether optical reactivation of tagged cocaine-related ensembles could substitute for a cocaine priming injection to reinstate CPP, whether reactivation altered cocaine-induced reinstatement, and if these effects differed depending on stage of drug exposure. We also compared these effects to reactivation of saline-associated ensembles. Cocaine produced robust locomotor activation during conditioning, and sensitization developed across repeated drug exposures. Reactivation of a cocaine-related engram alone did not reinstate CPP. However, reactivation of the first cocaine exposure engram attenuated cocaine-induced reinstatement. In contrast, reactivation of the fourth exposure engram did not confer this protective effect. Interestingly, reactivation of saline-associated ensembles also reduced cocaine-induced reinstatement specifically in females, suggesting dDG ensemble reactivation may modulate relapse-related behavior through interference or neuromodulatory disruption of cocaine-associated representations, consistent with our prior work. These findings raise the possibility that early contextual experiences form competing or destabilizing representations that interfere with later cocaine-seeking when reactivated. Females also displayed greater sensitivity to locomotor-inducing effects of cocaine memory reactivation, although this was dissociated from CPP. Together, these findings show that cocaine memories are distinct across drug experience and selective reactivation of dDG engrams can differentially influence drug-seeking.

Humans order numbers in space from left to right, with smaller quantities represented preferentially in the left hemispace and larger ones in the right hemispace. The direction of this mental number line (MNL), or more generally of number-space associations (NSA), is influenced by cultural habits such as reading and writing direction. However, a growing body of evidence from pre-verbal infants and non-human animals suggests that number-space mappings may also have biological foundations. In non-human primates, evidence for a directional MNL remains mixed, partly due to small sample sizes and methodological heterogeneity. Here, we tested samples of rhesus (Macaca mulatta) and crab-eating macaques (Macaca fascicularis) across two experiments using spontaneous food-related tasks. In Experiment 1, monkeys chose between identical food quantities (1x1 to 24x24) presented on the left and right. No systematic spatial choice bias emerged as a function of numerical magnitude, and hand use did not differ across exact numerical pairs, although exploratory analyses revealed magnitude-related modulations of manual responses. In Experiment 2, monkeys were habituated to small (4x4) or large (16x16) quantities and subsequently tested with the alternative quantity. Result showed significantly more leftward choices following numerical decreases (16[->]4) and more rightward choices following numerical increases (4[->]16), indicating that relative numerical context, rather than absolute magnitude, elicited directional spatial biases. These findings suggest that in macaques, number-space associations emerge most robustly in comparative contexts involving expectancy violations of magnitude.

Summary paragraphA hallmark of learning is the need for sensory stimuli (Ginns, 2015; McGraw et al., 2009; Reinwein, 2012; Spence, 1950) so that learning is fundamentally based on sensory input signals affecting behaviour, physiology, and neurology. If behavioural measures of learning can be causally linked to physiological and neurological variables, a broader understanding of the mechanisms related to learning in schools, learning disabilities, and learning and health issues may emerge (McGraw et al., 2009). Despite decades of research on the physiological/neurological variable of sympathetic activation, learning, and achievement (Horvers et al., 2021), any causal relation remains unclear (Cowley et al., 2014; Mason et al., 2020; Pijeira-Diaz et al., 2016; Sung et al., 2023; Yu et al., 2024) and issues with instrument validation remain (Costantini et al., 2023; Hu et al., 2024; Milstein & Gordon, 2020; Van Der Mee et al., 2021). Here we investigate the effect of sensory input on sympathetic activation by using validated instruments for skin conductance measurement (Batista et al., 2019) and whether sympathetic activation is connected to learning in a cognitive laboratory context and an ecologically valid classroom context. In both contexts, we found a physiological variable which correlated with learning and that sensory input affected this variable while student movement did not. These sensory inputs varied depending on the different instructional activities the students participated in. Together, these findings bring us one step closer to a model linking sensory input to behavioural, physiological, and neurological variables.

Linking environmental contexts with stressful experiences is critical for engaging adaptive responses necessary to avoid future threats. Yet, active context-dependent avoidance remains poorly understood. Here, we establish a restraint-induced conditioned place aversion (CPA) paradigm to examine how an acute physiological stressor acquires negative motivational value through contextual association. We found that mice repeatedly exposed to physical restraint in a contextually distinguishable chamber later avoid that location, demonstrating that restraint stress can drive learned aversion in the absence of continued exposure. To identify potential neuronal correlates underlying this learned association, we quantified c-Fos expression in several areas implicated in aversive motivation, emotional salience, and contextual encoding. We found that restraint within the context of the CPA paradigm was associated with increased c-Fos in the nucleus accumbens (NAc) and basolateral amygdala (BLA) while c-Fos expression increased in the ventral hippocampus in response to exposure to the contextual cues alone. These findings reveal region-specific engagement in processing aversive contextual memories induced by restraint stress. This work bridges classical stress models with associative learning frameworks, providing a platform to further dissect the neural mechanisms underlying stress-related negative affect and avoidance behaviors.

The Mnemonic Similarity Task (MST) is highly sensitive to age-related cognitive decline in humans and has been adapted for rodents using 3D objects, where aged animals show deficits in discriminating similar lures. To improve translational alignment with human testing and increase automation, we developed a touchscreen-based rat analog using a morphed Object-Cued Spatial Choice (OCSC) task with 2D image stimuli. Young (4-month) and aged (21-month) male and female Fischer 344 x Brown Norway hybrid rats were trained in Bussey-Saksida touchscreen chambers and tested on discrimination performance using image pairs that varied parametrically in feature overlap. We also assessed perirhinal cortical engagement in a subset of animals using Arc expression as a readout of activity-related principal cell firing following low-and high-overlap task epochs. Across shaping and procedural training, aged rats required more errors to reach criterion on one stimulus set, but both age groups successfully acquired the task. During morph testing, performance declined systematically as stimulus similarity increased, confirming that the task manipulated discrimination difficulty. However, contrary to expectations, young and aged rats performed similarly across overlap conditions, with no significant age-related impairment. In the Arc experiment, discrimination accuracy was again reduced by greater stimulus overlap, but Arc expression in perirhinal cortex did not differ reliably by age or overlap condition, although expression was associated with behavioral accuracy and deep layers showed higher ensemble similarity than superficial layers. These findings indicate that, while the touchscreen morph OCSC task is sensitive to stimulus similarity, it does not detect the robust age-related mnemonic discrimination deficits previously observed with 3D object-based rodent MST paradigms, underscoring the importance of considering ethological relevance when designing translational cognitive assays.

The dentate gyrus (DG) is thought to play a key role in the formation of dissociable memory representations for similar contexts. Neurons in the DG receive highly processed spatial and nonspatial sensory information from the medial and lateral entorhinal cortices, respectively. Changes in spatially tuned firing patterns of DG place cells occur after spatial changes to an environment, but the degree to which DG place cells respond to ethologically relevant nonspatial stimuli is largely unknown. Spatial and nonspatial information is thought to be transmitted to the DG during discrete local field potential events called dentate spikes. Here, we tested the extent to which different spatial and nonspatial stimuli modulate place cell firing patterns and dentate spike dynamics. We performed extracellular recordings of DG place cells and local field potentials in rats of both sexes exploring a familiar spatial environment, in which social stimuli and nonsocial odors of varying ethological relevance were presented, and a novel spatial environment. As expected, DG place cells exhibited different firing patterns between familiar and novel environments. Significant changes in firing were not observed, however, with any of the nonspatial stimuli. Surprisingly, the occurrence of dentate spikes associated with lateral entorhinal cortex input increased during exploration of ethologically relevant stimuli, and this increase was greater for social stimuli. Altogether, these results suggest that the DG preferentially responds to social stimuli at the network level, providing novel insights into how spatial and nonspatial information is processed in the DG. Significance StatementThe dentate gyrus (DG) encodes spatial and nonspatial sensory information. Here, we investigated how place cells in the DG respond to changes in spatial and nonspatial cues in familiar and novel environments in rats. We found that DG place cell firing patterns significantly changed in a novel spatial environment but did not significantly change when nonspatial stimuli were presented in a familiar environment. Conversely, discrete dentate spike events reflecting presumed nonspatial inputs from the lateral entorhinal cortex increased during investigation of ethologically relevant nonspatial stimuli. These findings suggest novel mechanisms of nonspatial information processing in the DG.

Subthreshold depression is associated with significant functional impairment and elevated risk of major depressive disorder. A negative self-concept may disrupt the implicit positive association evoked by ones own face, impairing incidental encoding of self-relevant information. Whether subthreshold depression involves a selective deficit in encoding self-face identity remains unclear. The attribute amnesia paradigm is well suited to address this question because it can dissociate attentional selection from working memory encoding. Using this paradigm, we examined the issue across two experiments. Experiment 1 employed nonsocial stimuli (animal drawings) and confirmed an intact attribute amnesia effect in subthreshold depression (n = 30) comparable to healthy controls (n = 30), ruling out a generalized encoding deficit. Experiment 2 replaced targets with faces (self or other) and revealed a selective enhancement of the attribute amnesia effect for self-face identity in subthreshold depression. Specifically, on the surprise trial, accuracy for self-face identity dropped to near-chance levels in the subthreshold depression group, whereas no such deficit emerged for other-faces or in controls. Encoding recovered rapidly once explicit memory expectations were introduced, indicating intact basic encoding capacity. These findings suggest that subthreshold depression is associated with a specific impairment in incidentally encoding self-face identity. This impairment likely stems from a negative self-concept that weakens self-face salience under incidental encoding conditions. By capturing this selective encoding failure, the present study reveals that the self-processing deficit in subthreshold depression can arise at the gating stage between attention and working memory consolidation.

Curiosity, a key driver of exploration and learning, is reinforced by reward-related neurochemical systems, yet the role of the opioidergic system in modulating this behavior remains unclear. Music, as a highly rewarding stimulus, offers a unique context to investigate the neurochemical basis of curiosity, particularly the unexplored role of opioids in music-driven exploration. To fill this gap, we performed a double-blind within-subject pharmacological design, in which 26 participants received, in two different sessions, either a placebo or the opioid antagonist naltrexone. During each session, participants engaged in a music exploration/exploitation trade-off paradigm designed to assess their willingness to pay for exploring unfamiliar electronic music. Using logistic regression mixed-effects models, we found that while naltrexone did not affect overall curiosity ratings, it significantly reduced exploratory behavior in states of heightened curiosity. These findings suggest that the opioidergic system plays a critical role in regulating the relationship between curiosity and exploration, particularly in the context of novel and rewarding stimuli like music. Overall, the present research provides new and compelling evidence on the important relationship between curiosity and exploration and its regulation with the opioidergic neurotransmitter subsystem. Significance StatementThe present research aimed to advance our understanding of the neurochemical mechanisms underlying curiosity and information seeking. In our study, we employed a pharmacological design to examine the role of the opioidergic system in music-related exploration. Using a novel music exploration/exploitation paradigm, we found that while naltrexone, an opioid antagonist, did not affect baseline curiosity ratings, it markedly reduced exploratory behavior during high-curiosity states in the presence of potential monetary losses. These results provide new evidence that opioidergic modulation plays a critical role in regulating curiosity-driven exploration. This new evidence might be relevant in the future for better understanding how neurochemical systems shape learning, motivation, and affective responses in complex cognitive domains such as music.