Neurobiology of Learning and Memory最新文献

{"title":"C57BL/6 mouse substrain differences in the ontogeny of auditory fear","authors":"Hanista Premachandran ,&nbsp;Kanza Naveed ,&nbsp;Maithe Arruda-Carvalho","doi":"10.1016/j.nlm.2026.108165","DOIUrl":"10.1016/j.nlm.2026.108165","url":null,"abstract":"<div><div>Early life adversity is a major risk factor for mental disorders later in life. Genetic and individual differences modulate the impact of early life trauma and stress on adult mental health, emphasizing the importance of understanding how the early onset of individual differences may shape behavioral outcomes across life. In rodents, genetic differences can be studied using inbred rodent strains or substrains. While C57BL/6 mouse substrains differ in their adult fear behavior, it is unclear when in development these differences emerge. Here we compared the ontogenesis of remote auditory fear retrieval, spontaneous recovery and renewal in the mouse C57BL/6J (Jax, from Jackson Laboratories) and C57BL/6NTac (Taconic Biosciences) substrains spanning postnatal days (P)16, P18, P21, P25 and P30. Taconic male and female mice show an earlier onset of persistent auditory fear memory and spontaneous recovery (females only) compared to Jax mice. Male Taconic mice also display earlier onset of renewal compared to Jax males. These data identify ontogenetic differences in fear processing among C57BL/6 mouse substrains, highlighting how individual differences can contribute to altered behavioral phenotypes in early development.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"225 ","pages":"Article 108165"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147931931","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 essential elements of an ecological approach to Pavlovian conditioning","authors":"Michael Domjan","doi":"10.1016/j.nlm.2026.108164","DOIUrl":"10.1016/j.nlm.2026.108164","url":null,"abstract":"<div><div>Pavlov was primarily an experimentalist rather than a naturalist. Although he was mindful of what his dogs might encounter in their natural environment, he was primarily interested in experimental control and precision rather than ecological validity. I discuss three essential elements of an ecological approach. First, in an ecological study the conditioned stimulus or CS is not “neutral” or “arbitrary” but has an inherent or pre-existing relation to the unconditioned stimulus or US. Conditioning with such ecological CSs produces results that are often different from what occurs with arbitrary CSs. Second, an ecological approach is focused on how a CS alters responding to the unconditioned stimulus or US. Numerous examples of conditioned modification of responding to the unconditioned response or UR are described, along with mechanisms that involve CR/UR summation and Pavlovian sensitization of reactivity to the US. The adaptive significance of the latter has been directly demonstrated in studies of conditioned fertility. Third, an ecological approach considers Pavlovian conditioning as the fine tuning of complex behavior systems that evolved to accomplish major tasks of living such as avoiding predators, finding food, and successfully reproducing. In considering how Pavlovian conditioning may alter a behavior system, an ecological approach emphasizes both changes in efferents or behaviors as well as changes in afferents or sensitivity to stimuli that are relevant to the behavior system.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"225 ","pages":"Article 108164"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840813","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":"Dynamic regulation of neuronal vault trafficking and RNA cargo by the noncoding RNA, Vaultrc5","authors":"Mason R.B. Musgrove ,&nbsp;Laura J. Leighton ,&nbsp;Margaux Lebouc ,&nbsp;Wei-Siang Liau ,&nbsp;Alexander D. Walsh ,&nbsp;Paul R. Marshall ,&nbsp;Stephanie M. Heyworth ,&nbsp;Adekunle T. Bademosi ,&nbsp;Nathalie Hertrich ,&nbsp;Qiongyi Zhao ,&nbsp;Sachithrani U. Madugalle ,&nbsp;Ambika Periyakaruppiah ,&nbsp;Xiang Li ,&nbsp;Joshua W.A. Davies ,&nbsp;Haobin Ren ,&nbsp;Hao Gong ,&nbsp;Esmi L. Zajaczkowski ,&nbsp;Nathalie Dehorter ,&nbsp;Frederic Meunier ,&nbsp;Marina Mikhaylova ,&nbsp;Timothy W. Bredy","doi":"10.1016/j.nlm.2026.108161","DOIUrl":"10.1016/j.nlm.2026.108161","url":null,"abstract":"<div><div>Vaults are large ribonucleoprotein complexes of unknown function. Here, we report that the vault-associated noncoding RNA, Vaultrc5, is highly enriched at the synapse and is required for activity-dependent vault trafficking in primary cortical neurons. We have discovered that vaults are comprised of unique populations of coding and non-coding RNA, and that this cargo varies dynamically between subcellular compartments. In addition, Vaultrc5 knockdown at the synapse shifts the RNA cargo toward transcripts associated with immune surveillance, and Vaultrc5 knockdown, <em>in vivo,</em> leads to altered fear extinction learning. These findings suggest that the Vaultrc5 is critically involved in coordinating the experience-dependent trafficking of vaults and related RNA cargo, which may represent a novel feature of neuronal plasticity associated with learning and memory.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"225 ","pages":"Article 108161"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777285","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":"Beta-blocking Pavlov’s Bells: Propranolol attenuates compound extinction in an error-dependent manner","authors":"Ashleigh K. Brink ,&nbsp;Clizia E. Martini ,&nbsp;Laura H. Corbit","doi":"10.1016/j.nlm.2026.108169","DOIUrl":"10.1016/j.nlm.2026.108169","url":null,"abstract":"<div><div>One hundred years ago, Pavlov observed that omitting the reinforcer that was previously paired with a conditional stimulus resulted in a decrease in the conditional response evoked by that stimulus, a phenomenon labeled <em>extinction</em>. Notably, Pavlov found that extinction was not permanent and the conditional response could recover under a range of conditions. As extinction is the basis of many modern therapies, the aim of much current work is to identify ways to enhance its longevity. To this end, one strategy is compound extinction, where a combination of previously reinforced stimuli is presented together for the first time during extinction training. This treatment has been shown to enhance extinction learning, evidenced by reduced future spontaneous recovery. However, the mechanisms are not fully understood. Experiment 1 assessed whether the compound extinction effect is the result of increased expectation of reward generated by the compound of stimuli that is then violated, driving further learning, or more simply, whether the novelty of the compound is able to re-engage attention and thus promotes extinction without increasing prediction error. Experiment 2 tested whether the effects of the noradrenaline β-receptor antagonist propranolol, shown elsewhere to reduce the compound extinction effect, relate to prediction error or novelty. We found that, when equating the novelty of the stimulus compound, larger prediction error resulted in better extinction evidenced as reduced spontaneous recovery. Further, we found that propranolol reduced this effect suggesting that prediction error rather than novelty recruits noradrenergic signalling. Together our results identify behavioural and pharmacological strategies that can improve the long-term expression of extinction.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"225 ","pages":"Article 108169"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147931928","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":"Lateralisation and localisation of spatial and verbal associative recognition memory","authors":"Neri Baker ,&nbsp;Adam Bentvelzen ,&nbsp;Heather Francis ,&nbsp;Nicholas Badcock","doi":"10.1016/j.nlm.2026.108162","DOIUrl":"10.1016/j.nlm.2026.108162","url":null,"abstract":"<div><div>Episodic memory is the conscious recalling of past experiences. The neural underpinnings of this skill have long been of clinical interest, as deficits can be debilitating, including to those with temporal lobe pathology. This study sought to improve the assessment of those with unilateral temporal lobe pathology by comparing the localisation and lateralisation of successful spatial and verbal associative recognition memory using 3D time–frequency analysis and connectivity analysis of EEG data, while reducing perceptual confounds. Twenty right-handed participants aged 18 to 33 years were included. Average band-power analysis in eLORETA was used to compare verbal associative memory, spatial associative memory, and the resting state to identify the regions of interest for subsequent analyses. Time-frequency analyses were conducted for the inferior temporal, parahippocampal, inferior frontal, and middle occipital gyri. Phase-synchronisation was compared between conditions between 32 regions of interest. Material specific differences in neural synchrony were identified, with peak synchronisation around 1000 ms that was unique to verbal associative memory and mildly left-lateralised, compared with temporally diffuse and bilateral desynchronisation during spatial associative memory. However, overall, levels of local synchrony during verbal and spatial associative memory were more similar than different, with no compelling evidence for dissociation by material type or hemisphere. Differences in phase-synchronisation between verbal and spatial associative memory for theta and alpha oscillations suggested their role in long-range rather than local synchrony. Future research should focus on replication, further explore connectivity, and assess material-specific deficits in perceptual processing to identify deficits in memory processing.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"225 ","pages":"Article 108162"},"PeriodicalIF":1.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777338","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":"TrkB receptor antagonist ANA-12 impairs memory reconsolidation in novel object recognition task via regulation of hippocampal transcriptome","authors":"Peixuan Tan ,&nbsp;Xiao Fu ,&nbsp;Saiyue Lin ,&nbsp;Xu-Dong Yu ,&nbsp;Jingkang Luo ,&nbsp;Michal R. Baran ,&nbsp;James Reilly ,&nbsp;Zhiming He ,&nbsp;Xinhua Shu","doi":"10.1016/j.nlm.2026.108141","DOIUrl":"10.1016/j.nlm.2026.108141","url":null,"abstract":"<div><div>Memory reconsolidation is a re-stabilization phase in which memory is gradually changed from unstable to stable. This process is critical because unstable memories can be subject to modification or erasure if the reconsolidation phase is disrupted within a 6 h time window. TrkB signaling pathway plays a key role in regulating neurogenesis, neuronal differentiation, maturation and survival. Numerous studies have reported that the TrkB signaling pathway participates in memory acquisition, consolidation and storage, although its role in memory reconsolidation is not fully understood. ANA-12, as a type of TrkB receptor inhibitor, can regulate various pain behaviors and attenuate propofol-induced apoptosis by blocking the TrkB signaling pathway. In this study, we investigated the effect of ANA-12 on memory reconsolidation in a novel object recognition (NOR) task. The results showed that ANA-12 injection immediately after the reactivation phase of the NOR task inhibited memory reconsolidation, whereas ANA-12 injection 6 h after the reactivation phase had no effect on memory performance. ANA-12 injection 24 h after the sample phase, with no subsequent reactivation phase, had no effect on memory performance. Transcriptome analysis demonstrated that ANA-12 administration significantly upregulated 347 genes and downregulated 79 genes in the hippocampus, compared to vehicle-treated animals. Those differentially expressed genes are involved in a wide range of functional pathways, including neuroinflammation, neurotransmitter synthesis, metabolism and transport, and long-term potentiation, which are all linked to memory impairment. These findings indicate that ANA-12-induced impaired memory reconsolidation is associated with changes in multiple signaling pathways.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"224 ","pages":"Article 108141"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080221","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":"Performing a motor action enhances associative learning in the absence of choice","authors":"Frederike Beyer ,&nbsp;Emily Fitzgibbon ,&nbsp;Thessa M. Howaldt ,&nbsp;Martin Göttlich ,&nbsp;Ulrike M. Krämer","doi":"10.1016/j.nlm.2026.108139","DOIUrl":"10.1016/j.nlm.2026.108139","url":null,"abstract":"<div><div>Forming pavlovian associations is fundamental to human behaviour. From gambling to social interactions, rewards are frequently preceded by motor actions. While studies have shown that making a choice enhances reward learning, in many cases (e.g. playing a slot machine), actions are performed without control over outcomes. We investigated the impact of performing an action on reward processing and associative learning in the absence of choice. We used a task in which coloured houses were probabilistically associated with social reward or punishment. On a trial-wise basis, we randomised whether participants pressed a button prior to observing the outcome, or waited passively. Using fMRI we explored the impact of performing an action on reward processing. Contrary to our hypotheses, we did not find reward-related activity in the striatum, nor a modulation of striatal activity by performing an action. Instead, we found tentative evidence for enhanced reactivity to negative outcomes in active trials in areas associated with affective processing and memory formation. Cues predicting positive outcomes were associated with enhanced activity in the temporo-parietal junction and precuneus. In a second, behavioral study, we used a forced-choice task testing the formation of stimulus-outcome associations. Participants preferred stimuli associated with reward over those associated with punishment. Both approach and avoidance were enhanced for stimuli learned in active trials. These findings suggest that performing a motor action enhances pavlovian-type associative learning, and may facilitate the neural processing of outcomes. This has important implications for our understanding of human learning, as well as gambling and other reward-driven behaviours.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"224 ","pages":"Article 108139"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096871","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":"Communication between the medial frontal cortex and mediodorsal thalamus is required for timing performance in rats","authors":"Benjamin J. De Corte ,&nbsp;Kelsey A. Heslin ,&nbsp;Nathan S. Cremers ,&nbsp;John H. Freeman ,&nbsp;Krystal L. Parker","doi":"10.1016/j.nlm.2026.108142","DOIUrl":"10.1016/j.nlm.2026.108142","url":null,"abstract":"<div><div>Predicting when future events will occur is critical for adaptive behavior, yet the brain networks underlying this ability remain unclear. The prefrontal cortex (PFC) and its rodent analogue, the prelimbic cortex (PL), are known to support the ability to track time and execute decisions in anticipation of upcoming events. Given this, we can expand our understanding of the circuits involved in time-based behavior by looking for regions that interact with the PFC during timing tasks. The mediodorsal nucleus of the thalamus (MD) is a strong candidate, as it shares dense reciprocal connections with the PFC and is widely implicated in higher-order cognition. However, data implicating the.</div><div>MD itself in timing is still minimal, and to our knowledge, causal data directly implicating MD-PFC communication in timing is lacking entirely. To address this, we trained nineteen male Long Evans rats on a dual interval timing task requiring decision-making and tested the effects of reversibly inactivating the MD/PL individually or blocking communication between them using GABA-A receptor agonist, muscimol. All manipulations produced a similar deficit—flattening the characteristic Gaussian-shaped reponse curves while leaving overall response rates intact. Single-trial analyses revealed that this was not simply a broadening of temporally-controlled response bursts, but rather a fundatment breakedown in the canonical burst structure of timing behavior, with responses becoming more uniflormly distrubted across the trial. These findings further implicate the MD and PL in timing and, to our knowledge, provide the first causal evidence that communication between the MD and PFC is specifically required. More broadly, these findings add to growing evidence that MD-PFC interactions support higher-order cognition. Timing impairments are common in a variety of neuropsychiatric diseases including schizophrenia, Parkinson’s disease, autism, and bipolar disorder so this work provides key implications for the involvement of a novel MD-PFC pathway.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"224 ","pages":"Article 108142"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146137752","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 self and others: Personal relevance modulates neural correlates of encoding and retrieval","authors":"Maria M. Nowicka,&nbsp;Marta Paź,&nbsp;Anna Nowicka","doi":"10.1016/j.nlm.2026.108138","DOIUrl":"10.1016/j.nlm.2026.108138","url":null,"abstract":"<div><div>Relating information to oneself is an effective encoding strategy that increases the likelihood of remembering and recalling information. Evidence suggests that self-focused encoding results in enhanced brain activity compared to other encoding strategies. However, findings regarding the neural correlates underlying the retrieval of self-referentially encoded information have been inconsistent. The main aim of this ERP study was to investigate the neural correlates associated with the recognition of information encoded in reference to the self, personally relevant others (a close other), and personally irrelevant others (a famous person). We hypothesized that the pattern of ERP findings during encoding and retrieval would be modulated by the subjective significance of the other. Initially, participants determined whether trait adjectives were appropriate for describing the self, a close other, or a famous person, and later classified words as either old (previously encountered) or new. Self-focused encoding was associated with increased LPP amplitudes compared to both the close other and famous person conditions, which also differed from each other. At recognition, the amplitudes of the recollection-related LPC and monitoring-related RFE were higher for self-referentially encoded words compared to those encoded in relation to a famous person. However, there was no difference in LPC and RFE amplitudes between trait adjectives encoded in reference to the self and to a close other, suggesting that the subjective significance of newly encoded information shapes the recognition process.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"224 ","pages":"Article 108138"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145990112","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":"Dopamine alters motor learning performance in the presence and absence of feedback","authors":"Li-Ann Leow ,&nbsp;Ashley Huey-Ryu Tan ,&nbsp;Timothy J Carroll ,&nbsp;Rob Adam ,&nbsp;Paul E Dux ,&nbsp;Hannah L Filmer","doi":"10.1016/j.nlm.2026.108140","DOIUrl":"10.1016/j.nlm.2026.108140","url":null,"abstract":"<div><div>We often choose to learn motor skills not only because of some external reward, but also because motor learning, in and of itself, is satisfying. While dopamine is thought to drive reward-based motor learning, it remains unclear whether dopamine is implicated in motor learning under conditions ostensibly driven by intrinsic rewards/motivation (i.e., in the absence of extrinsic feedback or reward). Here, by pharmacologically manipulating dopamine using the dopamine precursor Levodopa, we investigated the role of dopamine in an explicit motor learning task guided by internally determined signals of performance success, by removing intrinsic feedback about task success. Specifically, we asked participants to strategically aim away from presented targets by various instructed angles: a form of explicit motor learning that contributes to performance in the classic visuomotor rotation task. In the feedback condition, targets jumped mid-movement by the instructed angle, such that success in target hitting depended on successfully aiming away by the instructed angle. In the no-feedback condition, intrinsic feedback about task success was removed by having targets disappear mid-movement, such that participants could not know if they succeeded at hitting the targets or not. We found that dopamine altered performance, both with and without task feedback about task success. This provides direct evidence for a role of dopamine in motor learning driven by internal task goals.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"224 ","pages":"Article 108140"},"PeriodicalIF":1.8,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146065614","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}