Neurobiology of Learning and Memory最新文献

{"title":"Engrams across diseases: Different pathologies – unifying mechanisms?","authors":"Greta Leonore Balmer ,&nbsp;Shuvrangshu Guha ,&nbsp;Stefanie Poll","doi":"10.1016/j.nlm.2025.108036","DOIUrl":"10.1016/j.nlm.2025.108036","url":null,"abstract":"<div><div>Memories are our reservoir of knowledge and thus, are crucial for guiding decisions and defining our self. The physical correlate of a memory in the brain is termed an engram and since decades helps researchers to elucidate the intricate nature of our imprinted experiences and knowledge. Given the importance that memories have for our lives, their impairment can present a tremendous burden. In this review we aim to discuss engram malfunctioning across diseases, covering dementia-associated pathologies, epilepsy, chronic pain and psychiatric disorders. Current neuroscientific tools allow to witness the emergence and fate of engram cells and enable their manipulation. We further suggest that specific mechanisms of mnemonic malfunction can be derived from engram cell readouts. While depicting the way diseases act on the mnemonic component – specifically, on the cellular engram – we emphasize a differentiation between forms of amnesia and hypermnesia. Finally, we highlight commonalities and distinctions of engram impairments on the cellular level across diseases independent of their pathogenic origins and discuss prospective therapeutic measures.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108036"},"PeriodicalIF":2.2,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GluA1-containing AMPA receptors are necessary for sparse memory engram formation","authors":"Thije S. Willems ,&nbsp;Hui Xiong ,&nbsp;Helmut W. Kessels ,&nbsp;Sylvie L. Lesuis","doi":"10.1016/j.nlm.2025.108031","DOIUrl":"10.1016/j.nlm.2025.108031","url":null,"abstract":"<div><div>Memory formation depends on the selective recruitment of neuronal ensembles into circuits known as engrams, which represent the physical substrate of memory. Sparse encoding of these ensembles is essential for memory specificity and efficiency. AMPA receptor (AMPAR) subunits, particularly GluA1, play a central role in synaptic plasticity, which underpins memory encoding. This study investigates how GluA1 expression influences the recruitment of neurons into memory engrams. Using global GluA1 knockout (GluA1^KO) mice, localized knockout models, and contextual fear-conditioning paradigms, we evaluated the role of GluA1 in memory formation and engram sparsity.</div><div>GluA1^KO mice exhibited impaired short-term memory retention but preserved 24-hour contextual memory. Despite this, these mice displayed increased expression of the immediate early gene Arc in hippocampal neurons, indicative of a denser engram network. Electrophysiological analyses revealed reduced synaptic strength in GluA1-deficient neurons, irrespective of Arc expression. Localized GluA1 knockout in the hippocampus confirmed that GluA1 deficiency increases neuronal recruitment into engrams, disrupting the sparse encoding typically observed in wild-type mice.</div><div>These findings demonstrate that GluA1-containing AMPARs constrain engram size, ensuring selective recruitment of neurons for efficient memory encoding. By regulating synaptic plasticity, GluA1 facilitates both the encoding and size of memory circuits. This study highlights the critical role of GluA1 in maintaining sparse engram formation and provides insight into mechanisms underlying memory deficits in conditions where synaptic composition is altered.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"218 ","pages":"Article 108031"},"PeriodicalIF":2.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brain-wide immunolabeling and tissue clearing applications for engram research","authors":"Alessandra Franceschini ,&nbsp;Michelle Jin ,&nbsp;Claire W. Chen ,&nbsp;Ludovico Silvestri ,&nbsp;Alessia Mastrodonato ,&nbsp;Christine Ann Denny","doi":"10.1016/j.nlm.2025.108032","DOIUrl":"10.1016/j.nlm.2025.108032","url":null,"abstract":"<div><div>In recent years, there has been significant progress in memory research, driven by genetic and imaging technological advances that have given unprecedented access to individual memory traces or engrams. Although Karl Lashley argued since the 1930s that an engram is not confined to a particular area but rather distributed across the entire brain, most current studies have focused exclusively on a single or few brain regions. However, this compartmentalized approach overlooks the interactions between multiple brain regions, limiting our understanding of engram mechanisms. More recently, several studies have begun to investigate engrams across the brain, but research is still limited by a lack of standardized techniques capable of reconstructing multiple ensembles at single-cell resolution across the entire brain. In this review, we guide researchers through the latest technological advancements and discoveries in immediate early gene (IEG) techniques, tissue clearing methods, microscope modalities, and automated large-scale analysis. These innovations could propel the field forward in building brain-wide engram maps of normal and disease states, thus, providing unprecedented new insights. Ultimately, this review aims to bridge the gap between research focused on single brain regions and the need for a comprehensive understanding of whole-brain engrams, revealing new approaches for exploring the neuronal mechanisms underlying engrams.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"218 ","pages":"Article 108032"},"PeriodicalIF":2.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374480","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 Rescorla-Wagner model: It is not what you think it is","authors":"Guillem R. Esber,&nbsp;Geoffrey Schoenbaum,&nbsp;Mihaela D. Iordanova","doi":"10.1016/j.nlm.2025.108021","DOIUrl":"10.1016/j.nlm.2025.108021","url":null,"abstract":"","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108021"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978800","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":"Effects of maternal separation on punishment-driven risky decision making in adolescence and adulthood","authors":"Grace L. Minnes,&nbsp;Anna J. Wiener,&nbsp;Audrey S. Pisahl,&nbsp;Elizabeth A. Duecker,&nbsp;Boula A. Baskhairoun,&nbsp;Sharoderick C. Lowe,&nbsp;Nicholas W. Simon","doi":"10.1016/j.nlm.2024.108016","DOIUrl":"10.1016/j.nlm.2024.108016","url":null,"abstract":"<div><div>Early life adversity (ELA) is associated with a multitude of neural and behavioral aberrations. To develop treatments to mitigate the effects of ELA, it is critical to determine which aspects of cognition are affected and when these disturbances manifest across the lifespan. Here, we tested the effects of maternal separation, an established rodent model of ELA, on punishment-driven risky decision-making longitudinally in both adolescence (25–55 days old) and adulthood (80–100 days old). Risk-taking was assessed with the Risky Decision-making Task, wherein rats choose between a small, safe reward and a large reward accompanied by an escalating risk of punishment (foot shock). We observed that rats exposed to maternal separation were more prone to risk-taking than controls during adolescence, and demonstrated reduced latency to make both risky and safe decisions. Interestingly, this augmented risk-taking was no longer evident in adulthood. Males and females displayed comparable levels of risk-taking during adolescence then diverged in adulthood, with adult males displaying a sharp increase in risk-taking. Finally, we observed that risk-taking changed across the lifespan in rats exposed to maternal separation, but not in control rats. Collectively, these data reveal that ELA engenders risk-taking in adolescence but not adulthood, and that sex differences in risky decision-making are not evident until adulthood. This has important implications for the development of both behavioral and biological treatments to improve decision-making during the vulnerable adolescent period.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108016"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872700","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":"Male rats choose higher doses of nicotine in anticipation of a future non-drug period","authors":"Timothy J. Hill,&nbsp;Nathan M. Holmes,&nbsp;Kelly J. Clemens","doi":"10.1016/j.nlm.2025.108020","DOIUrl":"10.1016/j.nlm.2025.108020","url":null,"abstract":"<div><div>Humans and animals use information about future access to rewards to influence their behaviour in the present, however the evidence for this is largely anecdotal. Here we use the nicotine intravenous self-administration paradigm to ask whether rats can use an auditory stimulus signalling a long (450 s) signalled time-out on the next trial to influence their nicotine intake in the present. Rats were trained to choose between low (15 µg/kg/infusion), medium (30 µg/kg/infusion) or high (60 µg/kg/infusion) doses of nicotine on any given trial. Trials either had a ‘light’ trial with no tone and a standard 20 s post-infusion time-out, a ‘short-tone’ trial where a tone was presented but the time-out remained at 20 s, or a ‘long-tone’ trial where a second tone played and was accompanied by a long 450 s time-out period. During training rats clearly showed that dose selection was based on both the dose on the previous trial and the latency between infusions. When tones were presented, rats shifted their preference from the low dose to the high dose when the long-delay tone was presented, and this choice was particularly pronounced when the rat had previously selected a low dose. Together these findings are the first evidence that rats can regulate their nicotine intake in the present in anticipation of a future non-drug period. This result is discussed with respect to theories of negative reinforcement.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108020"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overcoming boundary conditions for object location memory destabilization in male rats involves dopamine D1 receptor activation","authors":"Olivia S. O’Neill,&nbsp;Karley V. George,&nbsp;Emily P. Minard,&nbsp;Boyer D. Winters","doi":"10.1016/j.nlm.2024.108017","DOIUrl":"10.1016/j.nlm.2024.108017","url":null,"abstract":"<div><div>Consolidated long-term memories can undergo strength or content modification via protein synthesis-dependent reconsolidation. This is the process by which a reminder cue initiates reactivation of the memory trace, triggering destabilization. Older and more strongly encoded spatial memories can resist destabilization due to biological boundary conditions. The present study investigated the role of dopamine (DA) at D1 receptors (D1Rs) in object location memory destabilization and overcoming boundary conditions for older (“remote”; tested with a 48-h rather than a 24-h delay between sample and reactivation) memory destabilization. Using male rats in a modified object location task, we found that administering the D1R antagonist SCH23390 (0.1 mg/kg, i.p.) prior to reactivation blocked destabilization of recently encoded memories, as well as novelty-induced destabilization of remote memories. Using remote parameters, systemically administered D1R agonist SKF38393 (5 mg/kg, i.p.) induced destabilization of remote object location memories in the absence of salient novelty. Intra-dorsal hippocampus administration of SCH23390 (2 μg/μL) also blocked destabilization of remote object location memories when a salient novel cue was present. These results are consistent with previous findings implicating DA in memory destabilization as well as demonstrate a role for D1-receptor activation in the destabilization of boundary condition protected-object location memories.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108017"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854708","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":"Cholinergic regulation of decision making under risk of punishment","authors":"Megan Kelly ,&nbsp;Merrick Garner ,&nbsp;Emily M. Cooper ,&nbsp;Caitlin A. Orsini","doi":"10.1016/j.nlm.2024.108018","DOIUrl":"10.1016/j.nlm.2024.108018","url":null,"abstract":"<div><div>The ability to choose between options that differ in their risks and rewards depends on brain regions within the mesocorticolimbic circuit and regulation of their activity by neurotransmitter systems. Dopamine neurotransmission in particular plays a critical role in modulating such risk-taking behavior; however, the contribution of other major modulatory neurotransmitters, such as acetylcholine, is not as well-defined, especially for decision making in which the risk associated with more rewarding outcomes involves adverse consequences. Consequently, the goal of the current experiments was to examine how cholinergic signaling influences decision making involving risk of explicit punishment. Male and female rats were trained in a decision-making task in which they chose between a small safe food reward and a larger food reward accompanied by a risk of footshock punishment. After training in this task, the effects of nicotinic and muscarinic agonists and antagonists on risk-taking performance were evaluated. Neither nicotine, a nicotinic receptor agonist, nor mecamylamine, a nicotinic receptor antagonist, affected preference for the risky lever, although mecamylamine did alter latencies to press the risky lever and the percentage of omissions. The muscarinic receptor agonist oxotremorine decreased preference for the large, risky lever; similar effects on behavior were observed with the administration of the muscarinic receptor antagonist scopolamine. Control experiments were therefore conducted in which these same muscarinic receptor ligands were administered prior to testing in a reward discrimination task. These experiments revealed that the effects of oxotremorine and scopolamine on risk taking may be due to altered motivational processes rather than to changes in sensitivity to risk of punishment. Importantly, there were no sex differences in the effects of cholinergic manipulations on preference for the large, risky lever. Collectively, these findings suggest that in both males and females, cholinergic signaling via muscarinic receptors is involved in decision making involving risk of explicit punishment, with a specific role in modulating sensitivity to differences in reward magnitude. Future studies will expand upon this work by exploring whether targeting cholinergic receptors has therapeutic potential for psychiatric conditions in which risk taking is pathologically altered.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108018"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877509","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":"Aversive social learning with a dead conspecific is achieved by Pavlovian conditioning in crickets","authors":"Kohei Hashimoto ,&nbsp;Kanta Terao ,&nbsp;Makoto Mizunami","doi":"10.1016/j.nlm.2024.108019","DOIUrl":"10.1016/j.nlm.2024.108019","url":null,"abstract":"<div><div>Social learning, learning from other individuals, has been demonstrated in many animals, including insects, but its detailed neural mechanisms remain virtually unknown. We showed that crickets (<em>Gryllus bimaculatus</em>) exhibit aversive social learning with a dead conspecific. When a learner cricket was trained to observe a dead cricket on a drinking apparatus, the learner avoided the odor of that apparatus thereafter. Here we investigated the hypothesis that this social learning is achieved by first-order Pavlovian conditioning of an odor (conditioned stimulus) and a dead conspecific (unconditioned stimulus, US). Injection of a dopamine receptor antagonist (flupentixol) before training or testing impaired the learning or execution of the response to the learned odor, as we reported in aversive non-social Pavlovian conditioning in crickets. Moreover, crickets that were trained with a dead conspecific and then received revaluation of the dead conspecific by pairing it with water reward exhibited an appetitive conditioned response (CR) to the odor paired with the dead conspecific. This suggests that execution of the CR is governed by the current value of the US as in non-social Pavlovian conditioning. In addition, we previously suggested that appetitive social learning with a living conspecific is based on second-order conditioning (SOC), and here we showed that SOC is achieved when crickets experienced pairing of a dead conspecific with water reward before experiencing social learning training with a dead conspecific. We conclude that social learning with a dead conspecific is based on Pavlovian conditioning and that this learning can be extended to second-order social learning.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"217 ","pages":"Article 108019"},"PeriodicalIF":2.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142896243","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":"How predictability and individual alpha frequency shape memory: Insights from an event-related potential investigation","authors":"Sophie Jano ,&nbsp;Alex Chatburn ,&nbsp;Zachariah R. Cross ,&nbsp;Matthias Schlesewsky ,&nbsp;Ina Bornkessel-Schlesewsky","doi":"10.1016/j.nlm.2024.108006","DOIUrl":"10.1016/j.nlm.2024.108006","url":null,"abstract":"<div><div>Prediction and memory are strongly intertwined, with predictions relying on memory retrieval, whilst also influencing memory encoding. However, it is unclear how predictability influences explicit memory performance, and how individual neural factors may modulate this relationship. The current study sought to investigate the effect of predictability on memory processing with an analysis of the N400 event-related potential in a context extending beyond language. Participants (<em>N</em> = 48, females = 33) completed a study-test paradigm where they first viewed predictable and unpredictable four-item ‘ABCD’ sequences of outdoor scene images, whilst their brain activity was recorded using electroencephalography. Subsequently, their memory for the images was tested, and N400 patterns during learning were compared with memory outcomes. Behavioural results revealed better memory for images in predictable sequences in contrast to unpredictable sequences. Memory was also strongest for predictable images in the ‘B’ position, suggesting that when processing longer sequences, the brain may prioritise the data deemed most informative. Strikingly, greater N400 amplitudes during learning were associated with enhanced memory at test for individuals with low versus high individual alpha frequencies. In light of the relationship between the N400 and stimulus predictability, this finding may imply that predictive processing differs between individuals to influence the extent of memory encoding. Finally, exploratory analyses provided evidence for a later positivity that was predictive of subsequent memory performance. Ultimately, the results highlight the complex and interconnected relationship between predictive processing and memory, whilst shedding light on the accumulation of predictions across longer sequences.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"216 ","pages":"Article 108006"},"PeriodicalIF":2.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}