Neurobiology of Learning and Memory最新文献

{"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}

{"title":"The molecular and cellular basis of memory engrams: Mechanisms of synaptic and systems consolidation","authors":"Janina Kupke ,&nbsp;Ana M.M. Oliveira","doi":"10.1016/j.nlm.2025.108057","DOIUrl":"10.1016/j.nlm.2025.108057","url":null,"abstract":"<div><div>The capacity to record and store life experiences for periods ranging from days to a lifetime is what allows an individual to adapt and survive. Memory consolidation is the process that drives the stabilization and long-term storage of memory and takes place at two levels – synaptic and systems. Recently, several studies have provided insight into the processes that drive synaptic and systems consolidation through the characterization of the molecular, functional and structural changes of memory engram cells at distinct time points of the memory consolidation process. In this review we summarize and discuss these recent findings that have allowed a significant step forward in our understanding of how episodic memory is formed and stored in engram cells of the hippocampus and the medial prefrontal cortex.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108057"},"PeriodicalIF":2.2,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864751","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":"DREADD-mediated inhibition of anterior retrosplenial cortex: Effects on novelty recognition of objects, locations, and object-in-place associations in male and female Long Evans rats","authors":"Dan L. McElroy,&nbsp;Ilne L. Barnard,&nbsp;Aiden E. Glass,&nbsp;Kaylen M. Young,&nbsp;Veronica Kryachko,&nbsp;Justin J. Botterill,&nbsp;John G. Howland","doi":"10.1016/j.nlm.2025.108055","DOIUrl":"10.1016/j.nlm.2025.108055","url":null,"abstract":"<div><div>Previous research suggests ionotropic glutamate receptors in anterior retrosplenial cortex (aRSC) are important for short-term (1-hour) object-in-place (OiP) novelty recognition, indicated by enhanced interaction with novel object-location pairs during OiP test phases. Here, male and female rats were repeatedly tested in three 1-hour delay novelty recognition tests: object recognition (OR), object location (OL), and OiP. Prior to behavioral testing, control (AAV5-CaMKIIα-mCherry) or active (AAV5-CaMKIIα-hM4D(Gi)-mCherry) viral vectors were bilaterally infused into the aRSC of male (8 control, 13 active) and female (8 control, 13 active) Long Evans rats, enabling selective inhibition of aRSC neurons with the hM4D agonist Compound 21 (C-21). Following recovery from surgery, rats were repeatedly tested in recognition tests following injection of either saline or C-21 (1.0 mg/kg; i.p.) ∼45-min prior to test phases (6 tests/rat). Analyses of exploration times indicated that total object interaction times did not differ between phase, sex, or treatment. Further analyses revealed that C-21 treatment of rats infused with the active vector reduced novelty recognition in the OR test yet had no influence in the OL test, regardless of sex. Interestingly, C-21 also reduced novelty recognition in OiP recognition test phases, an effect only observed in male rats infused with the active vector. Findings highlight a nuanced influence of aRSC neurons in supporting novelty recognition which varies by sex and type of stimuli assayed.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108055"},"PeriodicalIF":2.2,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143869838","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":"Sensitivity of associative priming to semantic relations: Insights from behavior and event-related potentials","authors":"Aiqing Nie ,&nbsp;Yuanying Wu ,&nbsp;Xia Zheng","doi":"10.1016/j.nlm.2025.108056","DOIUrl":"10.1016/j.nlm.2025.108056","url":null,"abstract":"<div><div>The priming effects have raised significant concerns. Previous research has solely focused on the priming of individual items, where both the prime and the target are single items. This study innovatively examines the priming effect for pairs and also considers the pair type for the target. In this experiment, the semantic relations of the prime and target pairs were categorized into thematic, taxonomic, and unrelated cases. The prime pairs were considered new, while the target pairs consisted of intact, rearranged, and “old + new” pairs. Behaviorally, we found that the priming effects were more pronounced when considering thematic relations compared to taxonomic relations. This indicates a stronger unitization between the items in taxonomic relations. Neurally, the N300 and N400 amplitudes were significantly larger for thematic relations compared to taxonomic relations. These results suggest that both object identification and semantic processing were more influenced by the semantic relation within the pairs. Moreover, we observed that the pair type exhibited distinct patterns in the ERP priming effect across different semantic relations. This indicates that semantic priming and repetition priming of associative pairs result in different effects.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108056"},"PeriodicalIF":2.2,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842805","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":"A long-term mild high-fat diet facilitates rabbit discrimination learning and alters glycerophospholipid metabolism","authors":"Desheng Wang,&nbsp;Ezekiel A. Irewole,&nbsp;Logan D. Bays,&nbsp;MacKinzie D. Smith,&nbsp;Bernard G. Schreurs","doi":"10.1016/j.nlm.2025.108053","DOIUrl":"10.1016/j.nlm.2025.108053","url":null,"abstract":"<div><div>Previous reports have shown an association between a Western high-fat diet (HFD) and poor cognitive performance. So far, there are no reports of whether a mild HFD can affect rabbit learning and hippocampal metabolic profile. This study was designed to explore whether feeding a mild HFD (5 % lard and 5 % soy oil) for 20 weeks affected eyeblink discrimination and discrimination reversal learning and hippocampal metabolic profiles. After 20 weeks on the HFD or a normal control diet, all rabbits received one day of adaptation, 20 daily sessions of two-tone discrimination (1-kHz CS + followed by air puff and 8-kHz CS- not followed by air puff), a rest day, and then 40 daily sessions of discrimination reversal (8-kHz CS + and 1-kHz CS-). Compared to rabbits fed a regular chow diet, rabbits fed a mild HFD showed better discrimination evidenced by higher responding to CS+, lower responding to CS-, and a larger discrimination index (CS+ − CS-). Widely targeted metabolomics analysis identified 1805 metabolites in the hippocampus, and significant HFD-induced changes in 162 and 165 differential metabolites in males and females, respectively. These included glycerophospholipids and fatty acyls. KEGG enrichment analysis showed glycerophospholipid metabolism (ko00564) was significantly enriched in the HFD group notably lysophosphatidylethanolamine and lysophosphatidylcholine. In summary, our data show a long-term mild HFD facilitated discrimination learning in rabbits without inducing a metabolic syndrome, and altered the hippocampal metabolic profile, which may affect neuronal cell membrane lipids and behavioral performance.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108053"},"PeriodicalIF":2.2,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839572","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 impairments observed after a half night sleep restriction are not mediated by working memory, attention, or inhibitory control mechanisms","authors":"Pim R.A. Heckman ,&nbsp;Robbert Havekes ,&nbsp;Arjan Blokland","doi":"10.1016/j.nlm.2025.108054","DOIUrl":"10.1016/j.nlm.2025.108054","url":null,"abstract":"<div><div>Sleep restriction is a growing issue in our modern society and thus it is crucial to uncover its neurocognitive consequences. Especially declarative memory is negatively affected by sleep loss due to its critical dependence on the hippocampus, a brain area known to be susceptible to sleep loss. Studies have shown that even a half night sleep restriction is sufficient to induce impairments in a range of hippocampus-dependent forms of memory. Nevertheless, memory performance is, at least to some extent, dependent on other cognitive functions. The aim of the current study was to reveal whether memory deficits observed after one night sleep deprivation, as observed in animal studies, translate to man, and whether these effects are mediated by impairments in other cognitive domains. We hypothesized that the memory paradigms would be affected but that, due to the short nature of the sleep restriction, this effect would not be mediated by other cognitive functions. To this end, fifty-five healthy participants conducted a test battery containing paradigms measuring verbal learning, spatial memory, attention, working memory, and response inhibition after a night of regular sleep or acute partial sleep restriction. The results of the study showed an impairment in both hippocampus-dependent memory tests, while no negative consequences of sleep deprivation were revealed on the other cognitive domains. In conclusion, our data indicate that the observed deficit in memory performance after a half night sleep deprivation is not mediated by impairments in attention (alerting, orienting, and executive control), working memory, or motor inhibitory control mechanisms.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108054"},"PeriodicalIF":2.2,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825785","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 formation following appetitive conditioning is variably dependent on retinoid signaling","authors":"Raymond K. Wong ,&nbsp;Gaynor E. Spencer","doi":"10.1016/j.nlm.2025.108048","DOIUrl":"10.1016/j.nlm.2025.108048","url":null,"abstract":"<div><div>Retinoic acid (RA), the metabolite of Vitamin A, plays an important role in central nervous system development and regeneration, as well as learning and memory in vertebrates. We have previously shown that RA signaling is also important for consolidation of long-term memory (LTM) in the invertebrate mollusc, <em>Lymnaea stagnalis</em>, following operant conditioning of the aerial respiratory behaviour. Here, we examine whether retinoids also play a role in classical reward conditioning in this mollusc. A single-trial appetitive conditioning paradigm was used, with amyl acetate as the conditioned stimulus (CS) and sucrose as the unconditioned stimulus (US). This produced an acquired conditioned response whereby the animal exhibited a feeding response to amyl acetate. A single-pairing of CS with US produced long-term memory at both 1d and 6d after training. Pharmacological treatments that disrupt RA signaling did not block the formation of long term memory when a 6-day food deprivation period was implemented before training. However, two different paradigms induced susceptibility of the conditioned response (memory) to retinoid signaling inhibitors. The first paradigm change involved using a shorter, 3-day food deprivation period in order to reduce motivational drive to feed, whereas the second paradigm manipulation reduced the strength of the unconditioned stimulus (sucrose). These findings suggest different susceptibility of memories to retinoid inhibition, depending on shifts in both external parameters of the experiment, as well as internal motivational states of the animal.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108048"},"PeriodicalIF":2.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143780619","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":"Glutamate receptor expression in the PL-BLA circuit is associated with susceptibility to showing the PTSD-like phenotype","authors":"Charlotte S. Rye ,&nbsp;Amy L. Milton","doi":"10.1016/j.nlm.2025.108051","DOIUrl":"10.1016/j.nlm.2025.108051","url":null,"abstract":"<div><div>While many individuals experience traumatic events during their lifetimes, only some go on to develop post-traumatic stress disorder (PTSD). This susceptibility and resilience to developing PTSD can be modelled in rodents using the stress-enhanced fear learning (SEFL) procedure, in which rats are exposed to a session of massed, unpredictable footshocks and subsequently assessed on tasks of adaptive fear learning. It has previously been observed that subpopulations of rats are susceptible and resilient to showing the PTSD-like phenotype following SEFL, and that these rats show differences in glutamate receptor expression in the basolateral amygdala. However, it is currently unknown whether structural differences are observed in other brain regions implicated in stress responding and memory. Using the refined SEFL procedure, this study aimed to determine whether expression of GluN2B, GluA1 and GluA2 receptor subunits in the prelimbic and infralimbic cortices, and dorsal hippocampus could be correlated to the SEFL-phenotype or shock experience in male rats. Here we show that following SEFL, differences can be observed in receptor subunit expression in the infralimbic cortex and dorsal hippocampus as a function of shock experience, whilst differences in the prelimbic cortex are associated with susceptibility. Importantly, these structural changes can be observed in male rats that are group-housed and exposed to 13-shocks rather than 15-shocks, indicating that the refined SEFL procedure offers a robust animal analogue of the non-associative fear sensitisation that occurs in PTSD. Future studies using this procedure could pave the way to the eventual development of pharmacological treatments to alleviate or prevent stress-induced psychopathology in susceptible individuals.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108051"},"PeriodicalIF":2.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738071","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}