Neurobiology of Learning and Memory最新文献

{"title":"Neural correlates of learning and memory are altered by early-life stress","authors":"","doi":"10.1016/j.nlm.2024.107952","DOIUrl":"10.1016/j.nlm.2024.107952","url":null,"abstract":"<div><p>The ability to learn and remember, which is fundamental for behavioral adaptation, is susceptible to stressful experiences during the early postnatal period, such as abnormal levels of maternal care. The exact mechanisms underlying these effects still remain elusive. This study examined whether early life stress (ELS) alters memory and brain activation patterns in male mice. Therefore, we examined the expression of the immediate early genes (IEGs) c-Fos and Arc in the dentate gyrus (DG) and basolateral amygdala (BLA) after training and memory retrieval in a fear conditioning task. Furthermore, we examined the potential of RU38486 (RU486), a glucocorticoid receptor antagonist, to mitigate ELS-induced memory deficits by blocking stress signalling during adolescence. Arc::dVenus reporter mice, which allow investigating experience-dependent expression of the immediate early gene Arc also at more remote time points, were exposed to ELS by housing dams and offspring with limited bedding and nesting material (LBN) between postnatal days (PND) 2–9 and trained in a fear conditioning task at adult age. We found that ELS reduced both fear acquisition and contextual memory retrieval. RU486 did not prevent these effects. ELS reduced the number of Arc::dVenus⁺ cells in DG and BLA after training, while the number of c-Fos⁺ cells were left unaffected. After memory retrieval, ELS decreased c-Fos⁺ cells in the ventral DG and BLA. ELS also altered the colocalization of c-Fos⁺ cells with Arc::dVenus⁺ cells in the ventral DG, possibly indicating impaired engram allocation in the ventral DG after memory retrieval. In conclusion, this study shows that ELS alters neuronal activation patterns after fear acquisition and retrieval, which may provide mechanistic insights into enduring impact of ELS on the processing of fear memories, possibly via changes in cell (co–) activation and engram cell allocation.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1074742724000637/pdfft?md5=17c53aa34668090e6951f2a6ce50a905&pid=1-s2.0-S1074742724000637-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141437224","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":"Olfactory investigation in the home cage","authors":"Andrew J.P. Fink ,&nbsp;Marcus Hogan ,&nbsp;Carl E. Schoonover","doi":"10.1016/j.nlm.2024.107951","DOIUrl":"10.1016/j.nlm.2024.107951","url":null,"abstract":"<div><p>We have developed a behavioral paradigm to study volitional olfactory investigation in mice over several months. We placed odor ports in the wall of a standard cage that administer a neutral odorant stimulus when a mouse pokes its nose inside. Even though animals were fed and watered <em>ad libitum</em>, and sampling from the port elicited no outcome other than the delivery of an odor, mice readily sampled these stimuli hundreds of times per day. This self-paced olfactory investigation persisted for weeks with only modest habituation following the first day of exposure to a given set of odorants. If an unexpected odorant stimulus was administered at the port, the sampling rate increased transiently (in the first 20 min) by an order of magnitude and remained higher than baseline throughout the subsequent day, indicating learned implicit knowledge. Thus, this system may be used to study naturalistic olfactory learning over extended time scales outside of conventional task structures.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1074742724000625/pdfft?md5=908c06737e4de0f7349035a2ace66ea3&pid=1-s2.0-S1074742724000625-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141267096","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":"Understanding sex differences and the translational value of models of persistent substance use despite negative consequences","authors":"Xavier J. Maddern ,&nbsp;Leigh C. Walker ,&nbsp;Roberta G. Anversa ,&nbsp;Andrew J. Lawrence ,&nbsp;Erin J. Campbell","doi":"10.1016/j.nlm.2024.107944","DOIUrl":"10.1016/j.nlm.2024.107944","url":null,"abstract":"<div><p>Persistent substance use despite negative consequences is a key facet of substance use disorder. The last decade has seen the preclinical field adopt the use of punishment to model adverse consequences associated with substance use. This has largely involved the pairing of drug use with either electric foot shock or quinine, a bitter tastant. Whilst at face value, these punishers may model aspects of the physical and psychological consequences of substance use, such models are yet to assist the development of approved medications for treatment. This review discusses progress made with animal models of punishment to understand the behavioral consequences of persistent substance use despite negative consequences. We highlight the importance of examining sex differences, especially when the behavioral response to punishment changes following drug exposure. Finally, we critique the translational value these models provide for the substance use disorder field.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1074742724000558/pdfft?md5=3d47a5bf27752888e1b4c02a7f39c1aa&pid=1-s2.0-S1074742724000558-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200180","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":"Behavioral outputs and overlapping circuits between conditional fear and active avoidance","authors":"Maria M. Diehl ,&nbsp;Justin M. Moscarello ,&nbsp;Sydney Trask","doi":"10.1016/j.nlm.2024.107943","DOIUrl":"10.1016/j.nlm.2024.107943","url":null,"abstract":"<div><p>Aversive learning can produce a wide variety of defensive behavioral responses depending on the circumstances, ranging from reactive responses like freezing to proactive avoidance responses. While most of this initial learning is behaviorally supported by an expectancy of an aversive outcome and neurally supported by activity within the basolateral amygdala, activity in other brain regions become necessary for the execution of defensive strategies that emerge in other aversive learning paradigms such as active avoidance. Here, we review the neural circuits that support both reactive and proactive defensive behaviors that are motivated by aversive learning, and identify commonalities between the neural substrates of these distinct (and often exclusive) behavioral strategies.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frustrative nonreward: Detailed c-Fos expression patterns in the amygdala after consummatory successive negative contrast","authors":"David Arjol ,&nbsp;Antonio D.R. Agüera ,&nbsp;Christopher Hagen ,&nbsp;Mauricio R. Papini","doi":"10.1016/j.nlm.2024.107942","DOIUrl":"10.1016/j.nlm.2024.107942","url":null,"abstract":"<div><p>The amygdala has been implicated in frustrative nonreward induced by unexpected reward downshifts, using paradigms like consummatory successive negative contrast (cSNC). However, existing evidence comes from experiments involving the central and basolateral nuclei on a broad level. Moreover, whether the amygdala’s involvement in reward downshift requires a cSNC effect (i.e., greater suppression in downshifted animals than in unshifted controls) or just consummatory suppression without a cSNC effect, remains unclear. Three groups were exposed to (1) a large reward disparity leading to a cSNC effect (32-to-2% sucrose), (2) a small reward disparity involving consummatory suppression in the absence of a cSNC effect (8-to-2% sucrose), and (3) an unshifted control (2% sucrose). Brains obtained after the first reward downshift session were processed for c-Fos expression, a protein often used as a marker for neural activation. c-Fos-positive cells were counted in the anterior, medial, and posterior portions (A/P axis) of ten regions of the rat basolateral, central, and medial amygdala. c-Fos expression was higher in 32-to-2% sucrose downshift animals than in the other two groups in four regions: the anterior and the medial lateral basal amygdala, the medial capsular central amygdala, and the anterior anterio-ventral medial amygdala. None of the areas exhibited differential c-Fos expression between the 8-to-2% sucrose downshift and the unshifted conditions. Thus, amygdala activation requires exposure to a substantial reward disparity. This approach has identified, for the first time, specific amygdala areas relevant to understand the cSNC effect, suggesting follow-up experiments aimed at testing the function of these regions in reward downshift.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141180134","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":"Disrupting dorsal hippocampus impairs category learning in rats","authors":"Matthew B. Broschard ,&nbsp;Jangjin Kim ,&nbsp;Bradley C. Love ,&nbsp;Hunter E. Halverson ,&nbsp;John H. Freeman","doi":"10.1016/j.nlm.2024.107941","DOIUrl":"10.1016/j.nlm.2024.107941","url":null,"abstract":"<div><p>Categorization requires a balance of mechanisms that can generalize across common features and discriminate against specific details. A growing literature suggests that the hippocampus may accomplish these mechanisms by using fundamental mechanisms like pattern separation, pattern completion, and memory integration. Here, we assessed the role of the rodent dorsal hippocampus (HPC) in category learning by combining inhibitory DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) and simulations using a neural network model. Using touchscreens, we trained rats to categorize distributions of visual stimuli containing black and white gratings that varied along two continuous dimensions. Inactivating the dorsal HPC impaired category learning and generalization, suggesting that the rodent HPC plays an important role during categorization. Hippocampal inactivation had no effect on a control discrimination task that used identical trial procedures as the categorization tasks, suggesting that the impairments were specific to categorization. Model simulations were conducted with variants of a neural network to assess the impact of selective deficits on category learning. The hippocampal inactivation groups were best explained by a model that injected random noise into the computation that compared the similarity between category stimuli and existing memory representations. This model is akin to a deficit in mechanisms of pattern completion, which retrieves similar memory representations using partial information.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140961903","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":"Excision of the endothelial blood–brain barrier insulin receptor does not alter spatial cognition in mice fed either a chow or high-fat diet","authors":"Joanne M. Gladding ,&nbsp;Neda Rafiei,&nbsp;Caitlin S. Mitchell,&nbsp;Denovan P. Begg","doi":"10.1016/j.nlm.2024.107938","DOIUrl":"10.1016/j.nlm.2024.107938","url":null,"abstract":"<div><p>Insulin is transported across the blood–brain barrier (BBB) endothelium to regulate aspects of metabolism and cognition. Brain insulin resistance often results from high-fat diet (HFD) consumption and is thought to contribute to spatial cognition deficits. To target BBB insulin function, we used Cre-LoxP genetic excision of the insulin receptor (InsR) from endothelial cells in adult male mice. We hypothesized that this excision would impair spatial cognition, and that high-fat diet consumption would exacerbate these effects. Excision of the endothelial InsR did not impair performance in two spatial cognition tasks, the Y-Maze and Morris Water Maze, in tests held both before and after 14 weeks of access to high-fat (or chow control) diet. The HFD increased body weight gain and induced glucose intolerance but did not impair spatial cognition. Endothelial InsR excision tended to increase body weight and reduce sensitivity to peripheral insulin, but these metabolic effects were not associated with impairments to spatial cognition and did not interact with HFD exposure. Instead, all mice showed intact spatial cognitive performance regardless of whether they had been fed chow or a HFD, and whether the InsR had been excised or not. Overall, the results indicate that loss of the endothelial InsR does not impact spatial cognition, which is in line with pharmacological evidence that other mechanisms at the BBB facilitate insulin transport and allow it to exert its pro-cognitive effects.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1074742724000492/pdfft?md5=274cd25a9fc64f7a78ba1af46a318369&pid=1-s2.0-S1074742724000492-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075192","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":"Consolidation of emotional memory during waking rest depends on trait anxiety","authors":"Lauren Hudachek ,&nbsp;Erin J. Wamsley","doi":"10.1016/j.nlm.2024.107940","DOIUrl":"10.1016/j.nlm.2024.107940","url":null,"abstract":"<div><p>A short period of eyes-closed waking rest improves long-term memory for recently learned information, including declarative, spatial, and procedural memory. However, the effect of rest on emotional memory consolidation remains unknown. This preregistered study aimed to establish whether post-encoding rest affects emotional memory and how anxiety levels might modulate this effect. Participants completed a modified version of the dot-probe attention task that involved reacting to and encoding word stimuli appearing underneath emotionally negative or neutral photos. We tested the effect of waking rest on memory for these words and pictures by manipulating the state that participants entered just after this task (rest vs. active wake). Trait anxiety levels were measured using the State-Trait Anxiety Inventory and examined as a covariate. Waking rest improved emotional memory consolidation for individuals high in trait anxiety. These results suggest that the beneficial effect of waking rest on memory extends into the emotional memory domain but depends on individual characteristics such as anxiety.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958592","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":"Recognizing the opponent: The consolidation of long-term social memory in zebrafish males","authors":"Luciano Cavallino ,&nbsp;María Florencia Scaia ,&nbsp;Andrea Gabriela Pozzi ,&nbsp;María Eugenia Pedreira","doi":"10.1016/j.nlm.2024.107939","DOIUrl":"10.1016/j.nlm.2024.107939","url":null,"abstract":"<div><p>Recognizing and remembering another individual in a social context could be beneficial for individual fitness. Especially in agonistic encounters, remembering an opponent and the previous fight could allow for avoiding new conflicts. Considering this, we hypothesized that this type of social interaction forms a long-term recognition memory lasting several days. It has been shown that a second encounter 24 h later between the same pair of zebrafish males is resolved with lower levels of aggression. Here, we evaluated if this behavioral change could last for longer intervals and a putative mechanism associated with memory storage: the recruitment of NMDA receptors. We found that if a pair of zebrafish males fight and fight again 48 or 72 h later, they resolve the second encounter with lower levels of aggression. However, if opponents were exposed to MK-801 (NMDA receptor antagonist) immediately after the first encounter, they solved the second one with the same levels of aggression: that is, no reduction in aggressive behaviors was observed. These amnesic effect suggest the formation of a long-term social memory related to recognizing a particular opponent and/or the outcome and features of a previous fight.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958593","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":"Pharmacological manipulations of the dorsomedial and dorsolateral striatum during fear extinction reveal opposing roles in fear renewal","authors":"Margaret K. Tanner ,&nbsp;Alyssa A. Hohorst ,&nbsp;Jessica D. Westerman ,&nbsp;Carolina Sanchez Mendoza ,&nbsp;Rebecca Han ,&nbsp;Nicolette A. Moya ,&nbsp;Jennifer Jaime ,&nbsp;Lareina M. Alvarez ,&nbsp;Miles Q. Dryden ,&nbsp;Aleezah Balolia ,&nbsp;Remla A. Abdul ,&nbsp;Esteban C. Loetz ,&nbsp;Benjamin N. Greenwood","doi":"10.1016/j.nlm.2024.107937","DOIUrl":"10.1016/j.nlm.2024.107937","url":null,"abstract":"<div><p>Systemic manipulations that enhance dopamine (DA) transmission around the time of fear extinction can strengthen fear extinction and reduce conditioned fear relapse. Prior studies investigating the brain regions where DA augments fear extinction focus on targets of mesolimbic and mesocortical DA systems originating in the ventral tegmental area, given the role of these DA neurons in prediction error. The dorsal striatum (DS), a primary target of the nigrostriatal DA system originating in the substantia nigra (SN), is implicated in behaviors beyond its canonical role in movement, such as reward and punishment, goal-directed action, and stimulus–response associations, but whether DS DA contributes to fear extinction is unknown. We have observed that chemogenetic stimulation of SN DA neurons during fear extinction prevents the return of fear in contexts different from the extinction context, a form of relapse called renewal. This effect of SN DA stimulation is mimicked by a DA D1 receptor (D1R) agonist injected into the DS, thus implicating DS DA in fear extinction. Different DS subregions subserve unique functions of the DS, but it is unclear where in the DS D1R agonist acts during fear extinction to reduce renewal. Furthermore, although fear extinction increases neural activity in DS subregions, whether neural activity in DS subregions is causally involved in fear extinction is unknown. To explore the role of DS subregions in fear extinction, adult, male Long-Evans rats received microinjections of either the D1R agonist SKF38393 or a cocktail consisting of GABA_A/GABA_B receptor agonists muscimol/baclofen selectively into either dorsomedial (DMS) or dorsolateral (DLS) DS subregions immediately prior to fear extinction, and extinction retention and renewal were subsequently assessed drug-free. While increasing D1R signaling in the DMS during fear extinction did not impact fear extinction retention or renewal, DMS inactivation reduced later renewal. In contrast, DLS inactivation had no effect on fear extinction retention or renewal but increasing D1R signaling in the DLS during extinction reduced fear renewal. These data suggest that DMS and DLS activity during fear extinction can have opposing effects on later fear renewal, with the DMS promoting renewal and the DLS opposing renewal. Mechanisms through which the DS could influence the contextual gating of fear extinction are discussed.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912557","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}