Neurobiology of Learning and Memory最新文献

{"title":"The interval between conditional stimulus onset and unconditional stimulus onset, not training-to-test interval, determines patterns of immediate early gene expression in the anterior retrosplenial cortex","authors":"Sydney Trask ,&nbsp;Jaden B. Brooks ,&nbsp;Sean Warner","doi":"10.1016/j.nlm.2025.108074","DOIUrl":"10.1016/j.nlm.2025.108074","url":null,"abstract":"<div><div>Prior work has found that the retrosplenial cortex (RSC) is necessary for formation and retrieval of trace, but not delay, fear conditioning. However, more recently, others have demonstrated that activity in the retrosplenial cortex is necessary for retrieval of a remotely-acquired delay fear memory, suggesting that as memory undergoes systems consolidation it becomes more dependent on neural activity in the RSC. Here, we aimed to examine expression of the immediate early gene zif268 in two distinct subregions of the retrosplenial cortex (anterior and posterior) following retrieval of either a recently-acquired or remotely-acquired delay fear memory. We found that while presenting the conditional stimulus either 1 day or 30 days following delay fear conditioning produced strong conditional responding, activity in either the anterior or posterior RSC assessed through expression of the immediate early gene zif268 was not elevated in the remote retrieval group, contrary to our hypothesis. Instead, activity in the pRSC was elevated in the group that received conditioning the day before. In line with some of our prior work, this suggests that animals in that group were showing neural activity in response to placement in a novel context. We then aimed to determine the circumstances under which delay fear retrieval could produce changes in the anterior RSC, which has been associated with conditional stimulus (CS) encoding and retrieval in a trace fear paradigm. We therefore compared delay and trace conditions to a delay conditioning procedure in which the CS and unconditional stimulus (US) onsets were matched to that of the trace procedure. We found that while both the trace and long-cue delay groups showed a similar behavioral pattern, with freezing that gradually extinguished throughout the 10-CS session, freezing in the standard delay group remained high. When examining zif268 activity, we found that while all three groups showed elevated zif268 expression in the pRSC, only the long-cue delay and trace groups showed increased aRSC activity. Interestingly, only the short-cue delay group showed increased zif268 activity in the basolateral amygdala, corresponding with their elevated fear behavior throughout the session. Together, these results suggest that zif268 activity in the RSC following conditioning is related to the interval between CS onset and US onset.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108074"},"PeriodicalIF":2.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The REM effect: How sleep stages influence learning strategies in complex reward-based decision-making","authors":"Eleni Kavaliotis ,&nbsp;Justin Mahlberg ,&nbsp;Daniel Bennett ,&nbsp;Antonio Verdejo-García ,&nbsp;Rowan P. Ogeil ,&nbsp;Sean P.A. Drummond","doi":"10.1016/j.nlm.2025.108072","DOIUrl":"10.1016/j.nlm.2025.108072","url":null,"abstract":"<div><div>Model-free (MF) and model-based (MB) learning strategies are complementary decision-making processes used in evaluating choices with potential rewards. Disorders involving compulsive behaviours (e.g., substance use, gambling) are suggested to emerge from an overreliance on MF learning, though the reasons for this bias remain unclear. Sleep disruptions, common in these disorders, could be a contributing factor, however no study has examined the impact of sleep and/or sleep loss on an individual’s engagement of each strategy. Thus, this study examined the influence of sleep on MF/MB learning in healthy adults. Participants (<em>n</em> = 67, M_age = 26.21yrs, SD = 5.82yrs, females = 65.67%) completed a two-stage reinforcement learning paradigm following a week of either sleep restriction (5-hr time in bed/night) or well-rested sleep (9-hr/night). Using mixed-effect logistic regressions and comprehensive computational modelling, we found no differences in MF and MB learning based on sleep condition (all <em>p</em> = &gt; 0.05). However, regressions showed less REM sleep was associated with increased use of MB learning, whilst greater levels of REM sleep were associated with increased use of MF learning. Computational modelling supported this, revealing negative associations between the MB parameter estimate and REM sleep percentage (<em>τ</em> = -0.22, <em>p</em> = 0.02). This suggests the amount of REM sleep prior to learning may potentially play a role in determining which strategy will dominate. In particular, individuals with less REM sleep may be less willing or able to assess the relative costs and benefits of each strategy. Future research should explore this relationship further.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108072"},"PeriodicalIF":2.2,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of biperiden on episodic memory: Testing the serial position effect","authors":"Arjan Blokland ,&nbsp;Laura Borghans ,&nbsp;Michal Hasselmo ,&nbsp;Anke Sambeth","doi":"10.1016/j.nlm.2025.108065","DOIUrl":"10.1016/j.nlm.2025.108065","url":null,"abstract":"<div><div>Biperiden (BIP), a muscarinic type 1 (M1) receptor antagonist, has been proposed as a pharmacological model for episodic memory impairment in mild cognitive impairment (MCI) and early stages of Alzheimer’s disease (AD). Understanding the effects of BIP on memory could also be relevant for the development of M1 agonists to improve memory. In this study, we specifically examined how BIP affected the serial position effect (SPE) in a word learning task. Since MCI and AD show memory deficits for the first words of a list (primacy effect) we predicted a similar effect for BIP. Data from four previous studies were collated in which the effects of BIP or placebo treatment was tested a double-blind randomized design. For testing the SPE effect, we calculated the average of the first 3 words (primacy), the last 3 words (recency) and the middle 10 words. To control for the level of performance in the different studies, z-scores were calculated. Overall, the analyses revealed a clear SPE effect. BIP did not impair the primacy or recency effect but was found to impair the memory for the middle 10 words in the delayed recall test. These findings indicate that blocking the M1 receptor not does impair the primacy or the recency effect in the SPE. Although BIP treatment has an overall impairing effect on episodic memory, it does not model primacy effect deficits in MCI and AD. However, M1 receptors appear to modulate the memory for weakly encoded/stored information suggesting that M1 agonist could improve verbal episodic memory.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108065"},"PeriodicalIF":2.2,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144190252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hormonal regulation of behavioral and emotional persistence: Novel insights from a systems-level approach to neuroendocrinology","authors":"Meenakshi M. Asokan,&nbsp;Annegret L. Falkner","doi":"10.1016/j.nlm.2025.108064","DOIUrl":"10.1016/j.nlm.2025.108064","url":null,"abstract":"<div><div>Gonadal sex steroid hormones regulate internal states, social drive, perception of external cues, and learning and memory. Fluctuating hormones influence mood and emotional states, enabling flexibility in instinctive behaviors and cognitive decisions. Conversely, elevated hormone levels help sustain emotional states and behavioral choices, ensuring the precise execution of costly social behaviors within optimal time windows to maximize reproductive success. While decades of work have shed light on the cellular and molecular mechanisms by which sex hormones alter neural excitability and circuit architecture, recent work has begun to tie many of these changes to principles of computation using the tools of systems neuroscience. Here, we will outline the mechanisms by which sex steroid hormones alter neural functioning at the molecular and cellular level and highlight recent work that points towards changes in specific computational functions, including the generation and maintenance of neural and behavioral persistence.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108064"},"PeriodicalIF":2.2,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144170405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Female rats retain goal-directed planning of action sequences after acute stress despite changes in planning structure and action sequence execution","authors":"Russell Dougherty ,&nbsp;Eric A. Thrailkill ,&nbsp;Sarah Van Horn ,&nbsp;Auny Kussad ,&nbsp;Donna J. Toufexis","doi":"10.1016/j.nlm.2025.108063","DOIUrl":"10.1016/j.nlm.2025.108063","url":null,"abstract":"<div><div>When making decisions under stress, organisms tend to deliberate less and rely on automatic habits. Prior investigation into the influence of stress on decision-making has primarily viewed goal-direction and habit as independent and competitive sources of control in static environments. The effects of acute stress on the integration of goal-direction and habit in hierarchical planning to solve dynamic tasks remain unclear. Here, our aim was to assess whether stress prompted the usage of habitual action sequences over the selection of discrete goal-directed actions in a serial decision task. We trained 16 female Long Evans rats in a two-stage binary choice task and performed two probe tests, one following acute restraint stress and one under control conditions, to identify how stress affected higher-level planning of behavior and intermediate action structures. We found that under both stressed and control conditions, rats exhibited goal-directed planning of habitual action sequences. However, following stress, rats showed a greater tendency to reiterate action sequences independent of reinforcement, indicating that stress may induce an aversion to exploration in action planning. Stress also increased the latency between responses – degrading action sequence integrity despite conserving their overall structure and performance. Taken together, these findings suggest that although acute stress does not disrupt the overall macrostructure of behavior in two-stage decision-making, it does alter the microstructure of goal-directed and habitual control individually. Further, these results imply that the extent to which stress impairs goal-direction in female rats may depend on the incentive structure and attentional demands of the decision environment.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108063"},"PeriodicalIF":2.2,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigations of forgetting in Caenorhabditis elegans","authors":"Man Zhu,&nbsp;Jiayi Wang,&nbsp;Ling Zhu,&nbsp;Man Zhu","doi":"10.1016/j.nlm.2025.108061","DOIUrl":"10.1016/j.nlm.2025.108061","url":null,"abstract":"<div><div>The traditional view considered forgetting as a passive process where memory traces gradually fade due to the natural weakening of neural connections. However, studies on olfactory memory in <em>Drosophila</em> have revealed that forgetting is an active process controlled by specific neural circuits. <em>Caenorhabditis elegans</em> is a widely used model organism in neurobiological research due to its relatively simple nervous system. Despite its simplicity, <em>C. elegans</em> exhibits complex behaviors influenced by environmental factors and prior experiences. Similar to <em>Drosophila</em>, <em>C. elegans</em> can actively initiate neural circuits based on the type of memory that needs to be forgotten, which supports using <em>C. elegans</em> as a model for studying forgetting. These characteristics facilitate the identification of genes and pathways involved in forgetting in <em>C. elegans</em>. In this review, we discuss recent advances in understanding forgetting mechanisms in <em>C. elegans</em> through three well-characterized olfactory learning paradigms. The insights derived from <em>C. elegans</em> offer a valuable framework for understanding the molecular and cellular mechanisms underlying forgetting, with potentially broader implications for memory regulation in more complex organisms.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108061"},"PeriodicalIF":2.2,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143935645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Memory processing by hippocampal adult-born neurons","authors":"Parimal Chavan ,&nbsp;Takashi Kitamura ,&nbsp;Masanori Sakaguchi","doi":"10.1016/j.nlm.2025.108062","DOIUrl":"10.1016/j.nlm.2025.108062","url":null,"abstract":"<div><div>This review provides an integrative overview of the functional roles of adult neurogenesis in the hippocampal dentate gyrus (DG), focusing specifically on its impact on memory processes across the lifespan. A distinguishing feature of this review is its systematic approach, organizing the contributions of adult-born neurons (ABNs) chronologically through the stages of memory—from initial encoding, through sleep-dependent consolidation, retrieval, and finally forgetting.</div><div>Although the existence and extent of adult neurogenesis in the human DG remain debated, accumulating evidence suggests that ABNs support cognitive functions throughout adulthood. This perspective gains particular importance when considering cognitive decline associated with aging and neurological disorders such as Alzheimer’s disease, which are linked to substantial reductions in adult neurogenesis.</div><div>We compare traditional models of DG function with emerging evidence highlighting both shared and unique contributions of ABNs. For example, the DG is well-established for its role in pattern separation, and as key mediators of this function, ABNs—due to their transiently heightened plasticity and excitability—appear critical for discriminating novel or similar experiences. On the other hand, recent findings underscore the distinct and essential role of ABNs in memory consolidation during REM sleep, suggesting specialized functions of ABNs that are absent in developmentally born granule cells in the DG.</div><div>Clinically, the potential therapeutic importance of enhancing neurogenesis in memory-related disorders, including post-traumatic stress disorder (PTSD), is emphasized, highlighting promising treatments such as memantine. Lastly, we outline key unresolved questions, advocating for future research aimed at understanding ABN-specific mechanisms. Far from being a mere evolutionary vestige, hippocampal ABNs represent dynamic and essential elements of neural plasticity that are critical for memory formation, adaptation, and resilience across the lifespan.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108062"},"PeriodicalIF":2.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic impact of early-life stress and prenatal immune activation on spatial memory and oxidative metabolism in rat cortico-limbic networks","authors":"Saúl Sal-Sarria ,&nbsp;Héctor González-Pardo ,&nbsp;Nélida M. Conejo","doi":"10.1016/j.nlm.2025.108060","DOIUrl":"10.1016/j.nlm.2025.108060","url":null,"abstract":"<div><div>Early life exposure to immune activation and stress are critical factors involved in the development of mental and neurodevelopmental disorders in adulthood. This study explored the individual and combined effects of prenatal lipopolysaccharide-induced (LPS)-induced immune activation and postnatal maternal separation on cognitive performance and oxidative metabolism in male Wistar rats. Using a 2 × 2 factorial design, pregnant dams were exposed to LPS or saline on gestational day 15, and offspring underwent maternal separation from postnatal days 2–14. In adulthood, cognitive function was assessed using the Morris Water Maze, and regional brain energy metabolism was evaluated using quantitative histochemistry of cytochrome <em>c</em> oxidase (CCO) quantitative histochemistry in the prefrontal cortex, hippocampus, and retrosplenial cortex.</div><div>Rats exposed to both stressors demonstrated significant impairments in spatial memory and cognitive flexibility, supporting the “two-hit” hypothesis of early adversity, which posits that early life exposure to an adverse environmental event (first hit) combined with subsequent exposure to stress during critical developmental periods (second hit) can significantly increase the risk of developing behavioral or neurodevelopmental disorders in adulthood. Accordingly, adult animals exposed to prenatal LPS and maternal separation showed prolonged escape latencies and decreased spatial memory retention during the behavioral tasks. Concurrently, CCO activity was markedly increased in all measured regions, reflecting heightened metabolic demands. These changes are consistent with impaired hippocampal-prefrontal-retrosplenial network integration and the underlying key processes involved in cognitive alterations such as memory or attention.</div><div>This study underscores the synergistic effects of these environmental factors on cognitive and metabolic dysfunction, providing a translational model to better understand the etiology of neurodevelopmental disorders. The findings highlight the importance of addressing multiple interacting environmental factors in the context of early life adversity.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108060"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Delayed emergence of EEG-based task-relevant representations","authors":"N. Menghi ,&nbsp;G. Melega ,&nbsp;A. Lidstrom ,&nbsp;L. Renoult ,&nbsp;W. Penny","doi":"10.1016/j.nlm.2025.108052","DOIUrl":"10.1016/j.nlm.2025.108052","url":null,"abstract":"<div><div>This paper examines the effect of a period of quiet wakefulness (an “offline wake” state) on the performance of a decision making task. An initial feedback-based learning period using a subset of stimuli, was followed by (i) a “pre-test” phase using both “old” and “new” stimuli without feedback, (ii) a delay period of either active or offline wakefulness, and (iii) a “post-test” period, again without feedback. Behaviourally, we found that offline wakefulness significantly improved generalization — the ability to apply learned knowledge to novel stimuli. However, we did not find any EEG-based neural correlates of this generalization improvement. Rather, we found that task-relevant representations emerged only after the delay period, independently of whether the delay was active or offline.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108052"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the role of BNST GABA neurons in backward conditioned suppression","authors":"Annie Ly,&nbsp;Hayden Hotchkiss,&nbsp;Emily D. Prévost,&nbsp;Julianne M. Pelletier,&nbsp;Melissa A. Deming,&nbsp;Luma Murib,&nbsp;David H. Root","doi":"10.1016/j.nlm.2025.108058","DOIUrl":"10.1016/j.nlm.2025.108058","url":null,"abstract":"<div><div>Conditioned suppression is a useful paradigm for measuring learned avoidance. In most conditioned suppression studies, forward conditioning is used where a cue predicts an aversive stimulus. However, backward conditioning, in which an aversive stimulus predicts a cue, provides unique insights into learned avoidance due to its influence on both conditioned excitation and inhibition. We trained mice to consume sucrose in context A, associated an aversive stimulus in context B to few or many forward or backwards paired cues (CS + ), and then tested for conditioned suppression in context A in response to the CS + . We found that few or many forward CS + and few backward CS + produced conditioned suppression, but many backwards cues did not. Administration of diazepam, a positive allosteric modulator of the GABA_A receptor, prevented conditioned suppression to the backward CS + but not to the forward CS + . Furthermore, freezing behavior was observed in response to the forward CS + but not the backward CS+, and diazepam had no effect on freezing or locomotion. We next examined BNST GABA neurons for potential sensitivity to backwards cues and conditioned suppression. VGaT BNST signaling increased in response to sucrose licks during the backward CS + but not to licks outside the CS + and not to the backward CS + onset or offset. Using designer receptors, we found that BNST VGaT neuron activation, but not its inhibition, prevented backward conditioned suppression expression. We conclude that backward conditioned suppression is dependent on both positive allosteric modulation of GABA on GABA_A receptors by diazepam and BNST GABA neurons.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108058"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}