Neurobiology of Learning and Memory最新文献

{"title":"The multiple faces of footshock punishment in animal research on addiction","authors":"Michel Engeln ,&nbsp;Serge H. Ahmed","doi":"10.1016/j.nlm.2024.107955","DOIUrl":"10.1016/j.nlm.2024.107955","url":null,"abstract":"<div><p>Continued drug use despite negative consequences is a hallmark of addiction commonly modelled in rodents using punished drug intake. Over the years, addiction research highlighted two subpopulations of punishment sensitive and resistant animals. While helpful to interrogate the neurobiology of drug-related behaviors, these procedures carry some weaknesses that need to be recognized and eventually defused. Mainly focusing on footshock-related work, we will first discuss the criteria used to define punishment-resistant animals and how their relative arbitrariness may impact our findings. With the overarching goal of improving our interpretation of the punishment-resistant phenotype, we will evaluate how tailored punishment protocols may better apprehend resistance to punishment, and how testing the robustness of punishment resistance could yield new results and strengthen interpretations. Second, we will question whether and to what extent punishment sensitivity, as currently defined, is reflective of abstinence and suggest that punishment resistance is, in fact, a prerequisite to model abstinence from addiction. Again, we will examine how challenging the robustness of the punishment-sensitive phenotype may help to better characterize it. Finally, we will evaluate whether diminished relapse-like behavior after repeated punishment-induced abstinence could not only contribute to better understand the mechanisms of abstinence, but also uniquely model progressive recovery (i.e., after repeated failed attempts at recovery) which is the norm in people with addiction. Altogether, by questioning the strengths and weaknesses of our models, we would like to open discussions on the different ways we interpret punishment sensitivity and resistance and the aspects that remain to be explored.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"213 ","pages":"Article 107955"},"PeriodicalIF":2.2,"publicationDate":"2024-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1074742724000662/pdfft?md5=a94a69fe50fa3ca32066060b92e65a47&pid=1-s2.0-S1074742724000662-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469657","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":"Effects of psilocybin on uncertain punishment learning","authors":"David S. Jacobs ,&nbsp;Alina P. Bogachuk ,&nbsp;Chloé L. Le Moing ,&nbsp;Bita Moghaddam","doi":"10.1016/j.nlm.2024.107954","DOIUrl":"10.1016/j.nlm.2024.107954","url":null,"abstract":"<div><p>Psilocybin may provide a useful treatment for mood disorders including anxiety and depression but its mechanisms of action for these effects are not well understood. While recent preclinical work has begun to assess psilocybin’s role in affective behaviors through innate anxiety or fear conditioning, there is scant evidence for its role in conflict between reward and punishment. The current study was designed to determine the impact of psilocybin on the learning of reward-punishment conflict associations, as well as its effects after learning, in male and female rats. We utilized a chained schedule of reinforcement that involved execution of safe and risky reward-guided actions under uncertain punishment. Different patterns of behavioral suppression by psilocybin emerged during learning versus after learning of risky action-reward associations. Psilocybin increased behavioral suppression in female rats as punishment associations were learned. After learning, psilocybin decreased behavioral suppression in both sexes. Thus, psilocybin produces divergent effects on action suppression during approach-avoidance conflict depending on when the conflict is experienced. This observation may have implications for its therapeutic mechanism of action.</p></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"213 ","pages":"Article 107954"},"PeriodicalIF":2.2,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443120","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":"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":"213 ","pages":"Article 107952"},"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":"213 ","pages":"Article 107951"},"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":"213 ","pages":"Article 107944"},"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":"213 ","pages":"Article 107943"},"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":"213 ","pages":"Article 107942"},"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":"212 ","pages":"Article 107941"},"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":"212 ","pages":"Article 107938"},"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":"212 ","pages":"Article 107940"},"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}