Neurobiology of Learning and Memory最新文献

{"title":"Neuro-immune interactions in memory.","authors":"E Stewart, T J Ryan","doi":"10.1016/j.nlm.2025.108077","DOIUrl":"https://doi.org/10.1016/j.nlm.2025.108077","url":null,"abstract":"<p><p>Responding appropriately to both internal and external factors to maintain homeostasis is key to survival in the dynamic environment we live in. Memory a is highly adaptive brain function which enables organisms to interact efficiently with their environment by processing and storing perceptual inputs. Memory shapes behaviour in the present based on past experiences. These experiences are defined by both external environmental cues and internal signals (physiological state) and this requires integration and feedback between central and peripheral systems. The immune system is a key physiological system that works to protect against pathogens and maintain homeostasis and can mediate behavioural changes through communication with the brain. Here we review the dynamic relationship between memory and the immune system in both health and disease.</p>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":" ","pages":"108077"},"PeriodicalIF":2.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144626768","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 role of post-learning EEG theta/beta ratio in long-term navigation performance","authors":"Roman Rozengurt ,&nbsp;Alexandra Doljenko ,&nbsp;Daniel A. Levy ,&nbsp;Avi Mendelsohn","doi":"10.1016/j.nlm.2025.108076","DOIUrl":"10.1016/j.nlm.2025.108076","url":null,"abstract":"<div><div>Memory consolidation processes have been shown to benefit from modulations in brain activity, particularly theta oscillations. Our previous studies showed that increases in post-learning Theta/Beta power ratio improves subsequent performance in both procedural and declarative memory across various tasks. In this study, we investigated the role of increases in frontal-midline Theta/Beta power ratio using EEG neurofeedback (NFB) in enhancing spatial memory consolidation during a navigation task in a virtual Minecraft environment. Sixty-four participants were randomly assigned to one of three groups: Theta/Beta NFB, Beta/Theta NFB, or a passive control group. Following spatial memory acquisition and three memory tests in the virtual environment, participants underwent a neurofeedback intervention designed to either upregulating or downregulate the Theta/Beta power ratio. Performance was assessed immediately post-intervention, 24 h later, and one week after the intervention. Results indicate that while some participants failed to regulate their Theta/Beta power by using the NFB display, those who increased their Theta/Beta power ratio, regardless of NFB, showed improved spatial memory, reflected in faster task completion times. Conversely, participants who exhibited a decrease in Theta/Beta ratio showed performance declines, while the passive control group showed minimal improvement. Although all participants improved over time, participants who increased Theta/Beta ratio showed the most substantial gains. These findings highlight the importance of post-learning Theta/Beta ratio oscillations in spatial memory consolidation. The study’s implications extend to clinical neuromodulation applications and a deeper understanding of memory processes.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108076"},"PeriodicalIF":2.2,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489700","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":"Increasing degradation-independent linear polyubiquitin in the hippocampus enhances memory in young adult but not aged rats","authors":"Morgan B. Patrick ,&nbsp;Natalie J. Preveza ,&nbsp;Yeeun Bae ,&nbsp;Harshini Venkat ,&nbsp;Olivia N. Ball ,&nbsp;Gueladouan Setenet ,&nbsp;Shannon E. Kincaid ,&nbsp;Jennifer R. Abraham ,&nbsp;Adam Cummings ,&nbsp;Anna Rubley ,&nbsp;W. Keith Ray ,&nbsp;Richard F. Helm ,&nbsp;Timothy J. Jarome","doi":"10.1016/j.nlm.2025.108075","DOIUrl":"10.1016/j.nlm.2025.108075","url":null,"abstract":"<div><div>Age-related memory loss affects approximately 40% of the world’s population after the age of 65 and is a significant risk factor for the development of dementia and Alzheimer’s Disease (AD). Numerous studies have reported that late in life there decreases in the function of the ubiquitin–proteasome system, the main regulator of protein degradation in cells that is also critically involved in memory formation. However, ubiquitin can mark proteins for fates other than destruction by the proteasome. Importantly, it remains unknown how the aging process alters proteasome-independent forms of ubiquitination and how this could contribute to age-related memory loss. Here, using an unbiased proteomic approach, we found that linear polyubiquitination – the only non-lysine proteasome-independent form of polyubiquitination – is significantly increased in the aged hippocampus at rest relative to young adults. However, in response to learning there was a significant reduction in linear polyubiquitination in the aged hippocampus, which contrasted with increases seen in young adult animals following learning. CRISPR-dCas9 mediated upregulation of linear polyubiquitination in the hippocampus improved memory in young adult, but not aged, rats. Together, these data suggest that while linear polyubiquitination is a critical regulator of hippocampus-dependent memory, increasing it in the aged hippocampus is not sufficient to improve memory in advanced age. These findings advance our understanding of the molecular mechanisms regulating memory late in life and stimulate future research on the role of degradation-independent ubiquitination in this process.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108075"},"PeriodicalIF":2.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365833","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":"Frustrative nonreward, sucrose consumption, and the basal ganglia: Role of chemogenetic activation of projections from the nucleus accumbens to the globus pallidus internus, globus pallidus externus, and ventral pallidum","authors":"Christopher W. Hagen,&nbsp;Jessica Suárez,&nbsp;Mauricio R. Papini","doi":"10.1016/j.nlm.2025.108073","DOIUrl":"10.1016/j.nlm.2025.108073","url":null,"abstract":"<div><div>Mammals experience negative emotions after the unexpected reduction in reward magnitude—called frustrative nonreward (FNR). The neurobiological mechanisms activated in response to unexpected reward downshift could shed light on loss-induced anxiety, conflict, mood, and physical pain. Experiment 1 examined the role of three basal ganglia (BG) pathways in the adjustment to unexpected sucrose downshifts. A double-infection chemogenetic procedure was used to activate neurons in the nucleus accumbens (NAc) that project to the globus pallidus externus (GPe), globus pallidus internus (GPi), or ventral pallidum (VP) during a 32-to-2% sucrose downshift. Activation of the NAc-to-GPe pathway had no observable effects on licking during reward downshift, whereas activation of either the NAc-to-GPi or NAc-to-VP pathways caused significant consummatory suppression. Chemogenetic activation of the NAc-to-GPi and NAc-to-VP pathways also yielded increased consummatory suppression in animals exposed to either 2% sucrose (Experiment 2) or 32% sucrose (Experiment 3) in the absence of a sucrose downshift. These effects were accompanied by no evidence of motor dysfunction in the open field and a nonsignificant trend toward a decrease in sucrose palatability, particularly with a choice between 2% sucrose and water. However, preliminary observations show that licking suppression after CNO injections also enhanced activity in the conditioning box during access to 32% sucrose and relative to vehicle injections. Thus, these BG pathways regulate consummatory behavior in different ways, but whether BG dysfunction influences the behavioral response to unexpected reward downshifts remains to be established.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"220 ","pages":"Article 108073"},"PeriodicalIF":2.2,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144314657","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 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}