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":"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":"2025-05-01","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":"2025-05-01","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":"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":"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":"2025-05-01","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":"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":"2025-05-01","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":"Modelling the acquisition of Pavlovian conditioning","authors":"Justin A Harris","doi":"10.1016/j.nlm.2025.108059","DOIUrl":"10.1016/j.nlm.2025.108059","url":null,"abstract":"<div><div>Pavlovian conditioning is a fundamental learning process that allows animals to anticipate and respond to significant environmental events. This review examines the key properties of the relationship between the conditioned stimulus (CS) and unconditioned stimulus (US) that influence learning, focussing on the temporal proximity of the CS and US, the spacing of trials (pairings of the CS and US), and the contingency between the CS and US. These properties have been touchstones for models of associative learning. Two primary theoretical approaches are contrasted here. Connection strength models, exemplified by the Rescorla-Wagner model (<span><span>Rescorla &amp; Wagner, 1972</span></span>), describe learning as trial-by-trial changes in the strength of an associative bond based on prediction errors. In time-based models of learning (e.g., <span><span>Gallistel &amp; Gibbon, 2000</span></span>) animals encode and remember temporal intervals and rates of reinforcement. The integration of Information Theory into time-based models (<span><span>Balsam &amp; Gallistel, 2009</span></span>) provides a mathematical framework for quantifying the effects of proximity, trial spacing, and contingency in terms of how much the CS reduces uncertainty about the US. The present paper incorporates a trial-by-trial Bayesian updating process into the information theoretic account to describe how uncertainty about the CS-US interval changes across conditioning. This Bayesian process is shown to account for empirical evidence about the way that responding changes continuously over conditioning trials.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108059"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917767","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":"2025-05-01","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":"The impact of systemic blockade of dopamine receptors on the acquisition of two-way active avoidance in male rats","authors":"L. Vercammen ,&nbsp;A. Lopez-Moraga ,&nbsp;T. Beckers ,&nbsp;B. Vervliet ,&nbsp;L. Luyten","doi":"10.1016/j.nlm.2025.108039","DOIUrl":"10.1016/j.nlm.2025.108039","url":null,"abstract":"<div><div>Active threat avoidance is a core aspect of adaptive and maladaptive behavior, yet its underlying mechanisms are not fully understood. Prior studies concluded that pharmacologically blocking dopaminergic receptors (DRs) disrupted avoidance acquisition, but it remains unclear whether such effects on learning persist during a drug-free follow-up test. To assess the involvement of D1R and D2R in avoidance acquisition, we conducted two experiments. In Experiment 1, thirty-six male Wistar rats underwent a single avoidance training session involving 30 tone-shock pairings. Rats could avoid the shock by moving to the opposite compartment of the shuttle box. Twenty minutes before training, rats received either D1R antagonist SCH<!--> <!-->23390 (0.05 mg/kg), D2R antagonist sulpiride (20 mg/kg), or vehicle. While sulpiride did not affect avoidance, 0.05 mg/kg SCH<!--> <!-->23390 significantly reduced the number of avoidance responses. In a separate test, 0.05 mg/kg SCH<!--> <!-->23390 also reduced locomotor activity. In Experiment 2 (N = 24), a lower dose of SCH<!--> <!-->23390 (0.025 mg/kg) was administered, and a drug-free avoidance test under continued reinforcement was added 24 h later to test for sustained effects of D1R blockade on avoidance in the absence of acute drug effects. Although animals avoided less with SCH<!--> <!-->23390 in the system, this effect did not persist 24 h later, suggesting that effects of D1R blockade during avoidance training might reflect an acute disruption of secondary processes involved in the performance of avoidance behavior rather than an actual impairment of avoidance learning.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"219 ","pages":"Article 108039"},"PeriodicalIF":2.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586404","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}