Learning & Memory

It is widely believed that starvation favours the processing of food-related cues, a notion here called the adaptive specificity hypothesis. Indeed, in Drosophila melanogaster starvation is required for appetitive odour-sugar but not for aversive odour-shock memory. Results from Gruber et al. (2013) and Meschi et al. (2024), however, suggest that starvation improves aversive short-term memory, too, challenging this hypothesis. We survey how starvation affects Drosophila associative olfactory short-term memory across 26 learning tasks. These tasks differ in the reinforcers and the amount of training, the life stage of the animals, in the predictive structure and associative timing of the task, in whether memory is expressed as an increase or decrease in odour preference, and in whether the learned behaviour is motivated by obtaining reward or avoiding/ escaping punishment. In adult flies, an improvement was observed for appetitive odour-sugar memories, whereas all tasks yielding aversive memory were unaffected. Strikingly, appetitive tasks that are not sugar-related, namely odour-shock extinction learning and punishment-relief associations, were either unaffected or even impaired, supporting the adaptive specificity hypothesis. In contrast, in 5-day-old larvae sugar-related appetitive associations were compromised, and the same was observed, to varying degrees, in larvae starved one day earlier and for aversive quinine associations, challenging the adaptive specificity hypothesis. Furthermore, we observed starvation-induced changes in locomotion and preference for a subset of the cues used in our study. Our results defy a simplistic interpretation in terms of the adaptive specificity hypothesis and call for case-by-case analyses of how starvation affects learning and behaviour.

Studies of visual discrimination in rodents can confound the effects of cue salience with reward value, making it difficult to determine which factor guides choice behavior. We examined this issue by testing how changes in relative salience affect decision dynamics in rats performing a two-alternative forced-choice task in which rats chose between visual cues associated with high or low sucrose rewards. After initial training with high and low luminance cues, we introduced a novel cue of intermediate luminance as a "luminance shift" test. The intermediate luminance cue substituted for either the brighter or dimmer cue and had the same reward value as the cue that it replaced. We found that while rats maintained a preference for the higher-value option, the introduction of a perceptually more similar cue consistently reduced choice preference and eliminated latency differences compared to baseline. Using drift diffusion modeling, we determined that the luminance shifts primarily caused a reduction in the drift rate (the speed of evidence accumulation), reflecting increased difficulty in cue discrimination. This finding suggests that the relative salience of the options determines the efficiency of evidence accumulation in value-based decisions. Furthermore, this effect on drift rate shows a dissociation from our previous work (Palmer et al., 2024), where prefrontal cortex inactivation specifically affected only the decision threshold. Our results demonstrate that relative salience influences deliberation, with low-level perceptual features shaping the computational dynamics of value-based choice. Our findings clarify the distinct contributions of sensory input and prefrontal function in the decision process. Significance StatementThis study reveals that changes in the relative salience of visual stimuli shape the computational dynamics of value-based decisions. We trained rats to make visually guided choices and found that relative differences in the brightness of the stimuli affect how quickly the rats made decisions and how often they chose a higher-value option. Our findings, together with a recent study on the role of the prefrontal cortex in value-guided decisions (Palmer et al., 2024), suggest that separate factors influence choice dynamics in rodents: visual salience affects the speed of deliberation, while prefrontal activity regulates caution. This study helps clarify how sensory and higher cognitive variables relate to the distinct computational components of the decision process.

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.

The platform-mediated active avoidance (PMA) task has been used as a rodent model of decision-based active avoidance in which rat learn to avoid a tone-signaled shock. Prior studies utilizing the PMA task have primarily investigated avoidance, freezing, and food-seeking behaviors, but few studies have thoroughly assessed darting behavior, a more recently identified measure of fear that has been largely explored in conditional fear paradigms. Here, we investigated the properties of darting that occur during the PMA task, in which rats either acquired the PMA task alone or with a social partner. We found that rats undergoing solitary PMA produced significantly more darting bouts, whereas rats undergoing social partner PMA produced darts that were faster and shorter in duration. We also found that darting in solitary PMA was predominantly concentrated at the platform, whereas darting in social partner PMA occurred more often outside of the platform and lever zones. Analysis of darting trajectories, which included movements surrounding each darting bout, revealed that darting was embedded in a broader movement strategy between the platform and lever zones, especially during solitary PMA, and this pattern increased across training days. These findings suggest that darting during the PMA task serves as a learned strategy to navigate between reward and safety and is modulated by social context, which is distinct from escape-like darting observed in auditory fear conditioning.

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.

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.

Memory interference occurs when an older memory competes with a newer memory that shares similar features 1. The hippocampal-entorhinal system is essential for memory 2,3, and the entorhinal cortex has been implicated in interference using the latent inhibition paradigm 4. In latent inhibition, prior non-reinforced exposure to a stimulus reduces the conditioned response later elicited when that same stimulus is paired with an aversive or appetitive outcome 5. Competition-based models propose that latent inhibition arises because the memory that the pre-exposed stimulus was inconsequential competes during retrieval with the memory that the same stimulus predicts an unconditioned stimulus 6. Although entorhinal cortex lesions or inactivation impair latent inhibition 7-10, the specific contribution of the lateral entorhinal cortex (LEC) remains unclear. The LEC provides non-spatial and cue-related input to the hippocampus 11 and has been implicated in associative memory 12,13. LEC function also declines with age 14,15, a period when memory interference increases 16. Here, we used chemogenetics to transiently inhibit excitatory neurons in the LEC during retrieval in a latent inhibition paradigm. LEC inhibition did not impair conditioned fear responses to a non-pre-exposed tone, indicating that retrieval of the tone-shock association remained intact. However, LEC inhibition attenuated latent inhibition by increasing conditioned fear responses to a pre-exposed tone. Together, these findings suggest that the LEC supports retrieval of prior inconsequential stimulus memories that compete with newer conditioned associations, providing a potential mechanism by which age-related LEC dysfunction may contribute to increased memory interference. HighlightsO_LIPre-exposure to a tone attenuates retrieval of a tone-evoked conditioned fear response, revealing latent inhibition C_LIO_LILateral entorhinal cortex inhibition does not impair fear-memory retrieval in non-pre-exposed animals C_LIO_LIThe lateral entorhinal cortex is required for the expression of latent inhibition during retrieval C_LIO_LIThe lateral entorhinal cortex contributes to memory interference during retrieval of stimuli with conflicting associations C_LI In BriefGhazy et al. show that the lateral entorhinal cortex (LEC) is required for latent inhibition during retrieval, in which prior tone exposure attenuates later fear responding to that same tone. Because LEC inhibition does not impair tone-evoked conditioned fear responding, these findings indicate that the LEC contributes to memory interference when the same stimulus has conflicting associations.

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.

RationaleAppetitive Pavlovian cues can drive maladaptive reward seeking via stimulus-reward memories. Disrupting memory reconsolidation offers a potential strategy to reduce their influence, but evidence for {beta}-adrenergic blockade with propranolol is inconsistent across behavioural paradigms, particularly relative to NMDA receptor antagonism. ObjectivesWe tested whether propranolol disrupts reconsolidation of appetitive sucrose memories in a discriminative goal-tracking paradigm, and compared its effects with those of the most commonly used NMDA receptor antagonist, MK-801. MethodsAdult Lister hooded rats underwent discriminative Pavlovian conditioning. Thirty minutes before a brief memory reminder (non-reinforced or reinforced), rats received systemic drug treatment or saline control. In study 1, MK-801 (0.1 mg/kg) was administered to male rats. In study 2, propranolol (10 mg/kg) was administered to equal numbers of male and female rats. Goal-tracking was tested drug-free at 1 and 8 days. ResultsIn study 1, MK-801 impaired subsequent discriminated responding at test. These effects were observed not only when reminder was non-reinforced as in previous successful demonstrations, but also with reinforced reminder. In study 2, Propranolol also impaired subsequent goal-tracking, regardless of reminder type, and the effects were consistent across sexes. ConclusionsPropranolol can disrupt reconsolidation of appetitive goal-tracking memories to a similar extent as MK-801 under conditions that promote memory destabilisation. These findings demonstrate that {beta}-adrenergic blockade can impair appetitive memory reconsolidation in a goal-tracking paradigm, challenging prior null findings and revitalising the potential for propranolol-based interventions in maladaptive reward-seeking behaviours.

Children often outperform adults in probabilistic statistical learning tasks, yet the mechanisms underlying this developmental advantage remain poorly understood. Here, we used eye-tracking measures of belief updating to examine how children and adults acquire and update predictions in a probabilistic sequence-learning task. Using the standard (oculomotor) reaction time measure, children showed stronger statistical learning than adults, replicating previous behavioral findings while revealing a more detailed profile of developmental differences in statistical learning. Critically, children updated their predictions more frequently: they were less likely to repeat previous predictions and more likely to shift their expectations in response to new input. Adults, in contrast, showed greater persistence, tending to maintain prior predictions even when those predictions were inconsistent with the underlying statistical structure. Despite these pronounced differences in updating behavior, the processing and use of prediction errors were remarkably similar across age groups. These findings indicate that developmental differences in statistical learning do not primarily arise from how prediction errors are computed, but rather from how prior beliefs and incoming information are weighted during belief updating. Children's enhanced learning may therefore reflect reduced reliance on stable priors and greater sensitivity to current sensory evidence, supporting a more exploratory learning strategy. Adults, by contrast, appear to favor an exploitative strategy that stabilizes existing predictions but reduces flexibility in probabilistic environments. More broadly, the results suggest that developmental changes in statistical learning may reflect age-related differences in how readily learners revise their predictions in response to incoming evidence. By integrating sensitive oculomotor measures with analyses that probe the mechanisms underlying belief updating, the present study provides a more fine-grained account of how predictive learning changes across development and offers a framework for reconciling previously inconsistent developmental findings in statistical learning.

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.

Considerable evidence suggests that the motivational control of instrumental action depends on incentive learning; i.e., on the opportunity to learn how the value of the consequences or outcome of an action, (e.g., a specific food) varies under different motivational conditions (e.g., under different degrees of hunger). The current study investigated whether learning the values of high-protein and high-carbohydrate rewards under different degrees of protein and carbohydrate appetite is also necessary for these nutrient-specific appetites to exert control over instrumental performance. Experiment 1 gave differing consummatory experience to whey protein and polycose carbohydrate outcomes under protein and carbohydrate appetite and found that, without the opportunity for incentive learning, the performance of actions earning these outcomes was insensitive to a shift in appetite. However, once the opportunity for incentive learning was provided, the rats increased their instrumental performance on a lever that earned the whey outcome relative to the polycose lever when protein hungry and on the polycose lever relative to the whey lever when carbohydrate hungry. Experiment 2 assessed how these nutrient-specific states exerted this control; whether, once learned, nutrient values were immediately controlled by nutrient appetite or whether this was based on conditional control acquired during experience with the outcomes under different nutrient appetites. We found that exposure to an outcome under a single nutrient-specific state was not sufficient to establish state-specific control. Instead, establishing the conditional control of outcome value required exposure to both the whey and polycose outcomes under both protein and carbohydrate appetites.

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.

Humans exhibit structured patterns of memory recall, including a tendency to recall more recent information and to recall events in the same order they were experienced. Classic computational models explain these patterns by positing that memories incorporate the ongoing ''temporal context'', formed by smoothly integrating the stimulus history. However, it is unclear whether a single mechanism can account for the full repertoire of human memory strategies, as the optimal approach may be task-dependent. For example, human memory experts widely apply the ''memory palace'' strategy, which is empirically better but not captured by temporal context models. Here we show that neural networks optimized for free recall develop diverse retrieval strategies, with only some of them resembling temporal context models.The best-performing models discovered a stimulus-invariant index code that emphasizes the studied position of each list item, instead of its temporal context. This creates a stable scaffold for forward recall akin to the memory palace technique. This index code was more likely to emerge when networks were i) encouraged to recall all studied items rather than prioritizing a few items, and ii) prevented from relying on recency, resonating with human data. Our findings demonstrate that human-like recall patterns can arise from multiple distinct computational mechanisms, and that sequential retrieval using item index is an optimal strategy that explains expert-level recall performance.

Forming associations between temporally separated events depends on pathways linking the CA1, the subiculum (SUB), and the entorhinal cortex. The degree to which this process requires the CA2, which shares extensive connectivity with these regions, remains unknown. Using trace fear conditioning (TFC), where mice learn to associate a tone and shock separated by a temporal gap, we showed that the dCA2 contributes to TFC. Interestingly, whereas chronic dCA2 inhibition decreased cue-associated freezing, acute dCA2[->]dCA1 projection inhibition increased freezing. Combined with differential effects on cFos expression, this suggests that global and projection-specific perturbations of the dCA2 have distinct effects on TFC and hippocampal activity states. Fiber photometry revealed that dCA2[->]dCA1 activity shifted from tone responsiveness during conditioning to expected shock activation during recall, consistent with learning-associated activity remodeling. Together, these findings identify the dCA2 as a contributor to TFC and implicate dCA2[->]dCA1 signaling in shaping fear expression across learning and recall.

Animals balance staying in a favorable environment with exploring new ones. In C. elegans chemotaxis, the process by which worms migrate toward an attractant has been extensively studied. However, what happens after they reach it remains largely unexplored, partly because conventional assays immobilize worms at the point of arrival. Here, we quantitatively analyzed chemotactic behavior upon reaching an attractive odor source using an immobilization-free chemotaxis assay. We observed that 62% animals left the isoamyl alcohol region after initially approaching it, a behavior we termed "leaving behavior." Quantitative analysis revealed that leaving behavior represents a distinct locomotor state compared with free-moving, high-concentration odor avoidance, and approach behavior. To test whether leaving behavior is related to olfactory adaptation, we analyzed mutants in adaptation-related genes. The proportion of leaving behavior was significantly increased in egl-4 loss-of-function mutants compared with wild-type animals, whereas arr-1 mutants showed no significant difference. These results suggest that egl-4 negatively regulates leaving behavior, suggesting a role for this kinase in stabilizing post-arrival behavioral states beyond its known function in olfactory adaptation. Our findings indicate that chemotaxis involves dynamic behavioral transitions even after reaching an attractant, consistent with an exploration-exploitation trade-off framework.

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.

High intra-individual reaction time variability (RTV) is traditionally viewed through a deficit perspective and interpreted as a maladaptive signature of attentional lapses, cognitive inefficiency, and systemic noise. However, theories from motor learning and the competitive neurocognitive networks framework suggest that behavioral variability and reduced top-down control might actually facilitate certain forms of implicit skill acquisition. The present study addresses the apparent conflict between these perspectives by investigating whether elevated RTV serves as an adaptive, functional precursor to implicit statistical learning. Across two independent studies, participants completed the Alternating Serial Reaction Time (ASRT) task. We quantified early RTV during the initial task phase using multiple metrics -- coefficient of variation, inter-trial RTV, and ex-Gaussian parameters Sigma and Tau-- to predict subsequent statistical learning. Analyses controlled for baseline response speed and early learning artifacts, and test-retest reliability measures were also evaluated. Our results show that early RTV predicted later statistical learning measured via reaction times. This predictive relationship was most consistent for metrics capturing dynamic, moment-to-moment fluctuations (inter-trial RTV and Sigma) rather than extreme attentional lapses (Tau). While the effect size was relatively small, the association remained significant after controlling for potential statistical confounds. Furthermore, early RTV demonstrated strong test-retest stability. These findings challenge the exclusively deficit-oriented perspective on behavioral noise. Instead, we propose that elevated RTV may reflect an adaptive, exploratory processing tendency, analogous to kinematic exploration in motor learning, that could support the brains ability to implicitly extract and model probabilistic environmental regularities.

The medial prefrontal cortex (mPFC) plays a significant role in modulating the threat response, particularly in ambiguous circumstances. The mPFC performs this role through its connectivity with multiple brain regions, including the amygdala, long regarded as the central hub for threat responses. However, the roles of specific prefrontal projections to the amygdala in contextual threat discrimination are not yet fully understood, particularly regarding more complex learning tasks and when disentangling the functionally distinct prelimbic (PL) subunit of the mPFC. Here, we challenged mice with a contextual differential threat conditioning (DTC) learning task in which subjects were repeatedly exposed to one context predictive of a foot shock (CS+) and to a similar yet distinct context that was not (CS-). While control mice showed a similar threat response in both contexts immediately after threat conditioning, within a few days of contextual exposures, controls acquire threat discrimination and freeze less to CS- than to CS+ during late DTC. However, we found that inducing localized hypofunction of neuroplasticity in PL neurons projecting to the basolateral amygdala (BLA) impairs performance on DTC. This finding identifies the specific population of neurons in PL cortices as a critical site for learning to discriminate threat.

It has been shown that early-life adversity (ELA) shapes how individuals learn, remember, and make decisions, yet the precise computations altered by these experiences remain unclear. Here, we combine a structured foraging task with computational modeling to test a recently developed theory for how a particular kind of ELA, early-life unpredictability (ELU), specifically influences choice under uncertainty. Adult participants (N=297) performed a sequential foraging task requiring continuous trade-offs between exploiting depleting resources and exploring alternatives. Subsets also completed assessments of early-life unpredictability (QUIC) and for trauma symptoms arising from lifelong stressors (PCL). We fit participants behavior with a Bayesian learning-and-planning model in which uncertainty modulates the valuation of leaving a current resource patch. Critically, the subjective influence of local uncertainty was allowed to vary freely between participants. Consistent with theoretical proposals, computational model fits and mediation analyses revealed a robust indirect pathway: ELU predicted increased discounting in the face of uncertainty, which in turn predicted greater overharvesting. This pattern was consistent across environmental conditions, indicating that early-life unpredictability primarily influences behavior through a general influence on uncertainty processing. Importantly, although PCL scores were also correlated with uncertainty adaptation, these effects were fully accounted for by shared variance with ELU, offering a clear dissociation between developmental unpredictability and lifelong traumatic experience. Together, our results show that early-life unpredictability causes long-lasting changes in decision-making by amplifying the subjective experience of uncertainty.