Learning & memory最新文献

{"title":"High stakes slow responding, but do not help overcome Pavlovian biases in humans","authors":"Johannes Algermissen, Hanneke E.M. den Ouden","doi":"10.1101/lm.054017.124","DOIUrl":"https://doi.org/10.1101/lm.054017.124","url":null,"abstract":"“Pavlovian” or “motivational” biases are the phenomenon that the valence of prospective outcomes modulates action invigoration: the prospect of reward invigorates actions, while the prospect of punishment suppresses actions. Effects of the valence of prospective outcomes are well established, but it remains unclear how the magnitude of outcomes (“stake magnitude”) modulates these biases. In this preregistered study (<em>N</em> = 55), we manipulated stake magnitude (high vs. low) in an orthogonalized Motivational Go/NoGo Task. We tested whether higher stakes (a) strengthen biases or (b) elicit cognitive control recruitment, enhancing the suppression of biases in motivationally incongruent conditions. Confirmatory tests showed that high stakes slowed down responding, especially in motivationally incongruent conditions. However, high stakes did not affect whether a response was made or not, and did not change the magnitude of Pavlovian biases. Reinforcement-learning drift-diffusion models (RL-DDMs) fit to the data suggested that response slowing was best captured by stakes prolonging the non-decision time. There was no effect of the stakes on the response threshold (as in typical speed-accuracy trade-offs). In sum, these results suggest that high stakes slow down responses without affecting the expression of Pavlovian biases in behavior. We speculate that this slowing under high stakes might reflect heightened cognitive control, which is however ineffectively used, or reflect positive conditioned suppression, i.e., the interference between goal-directed and consummatory behaviors, a phenomenon previously observed in rodents that might also exist in humans. Pavlovian biases and slowing under high stakes may arise in parallel to each other.","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"5 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142251691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding Arc transcription: a live-cell study of stimulation patterns and transcriptional output","authors":"Dong Wook Kim, Hyungseok C. Moon, Byung Hun Lee, Hye Yoon Park","doi":"10.1101/lm.054024.124","DOIUrl":"https://doi.org/10.1101/lm.054024.124","url":null,"abstract":"Activity-regulated cytoskeleton-associated protein (Arc) plays a crucial role in synaptic plasticity, a process integral to learning and memory. Arc transcription is induced within a few minutes of stimulation, making it a useful marker for neuronal activity. However, the specific neuronal activity patterns that initiate Arc transcription have remained elusive due to the inability to observe mRNA transcription in live cells in real time. Using a genetically encoded RNA indicator (GERI) mouse model that expresses endogenous Arc mRNA tagged with multiple GFPs, we investigated Arc transcriptional activity in response to various electrical field stimulation patterns. The GERI mouse model was generated by crossing the Arc-PBS knock-in mouse, engineered with binding sites in the 3′ untranslated region (UTR) of Arc mRNA, and the transgenic mouse expressing the cognate binding protein fused to GFP. In dissociated hippocampal neurons, we found that the pattern of stimulation significantly affects Arc transcription. Specifically, theta-burst stimulation consisting of high-frequency (100 Hz) bursts delivered at 10 Hz frequency induced the highest rate of Arc transcription. Concurrently, the amplitudes of nuclear calcium transients also reached their peak with 10 Hz burst stimulation, indicating a correlation between calcium concentration and transcription. However, our dual-color single-cell imaging revealed that there were no significant differences in calcium amplitudes between Arc-positive and Arc-negative neurons upon 10 Hz burst stimulation, suggesting the involvement of other factors in the induction of Arc transcription. Our live-cell RNA imaging provides a deeper insight into the complex regulation of transcription by activity patterns and calcium signaling pathways.","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"5 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety signals reinforce instrumental avoidance in humans","authors":"Courteney T.L. Fisher, Gonzalo P. Urcelay","doi":"10.1101/lm.053914.123","DOIUrl":"https://doi.org/10.1101/lm.053914.123","url":null,"abstract":"Safety signals reinforce instrumental avoidance behavior in nonhuman animals. However, there are no conclusive demonstrations of this phenomenon in humans. Using human participants in an avoidance task, Experiments 1–3 and 5 were conducted online to assess the reinforcing properties of safety signals, and Experiment 4 was conducted in the laboratory. Participants were trained with CSs+ and CSs–, and they could avoid an aversive outcome during presentations of the CSs+ by pressing their space bar at a specific time. If successful, the aversive outcome was not presented but instead a safety signal was. Participants were then tested—whilst on extinction—with two new ambiguous test CSs. If participants made an avoidance response, one of the test CSs produced the trained safety signal and the other was a control. In Experiments 1 and 4, the control was followed by no signal. In Experiment 2, the control was followed by a signal that differed in one dimension (color) with the trained safety signal, and in Experiment 3, the control differed in two dimensions (shape and color) from the trained safety signal. Experiment 5 tested the reinforcing properties of the safety signal using a choice procedure and a new response during test. We observed that participants made more avoidance responses to the ambiguous test CSs when followed by the trained signal in Experiments 1, 3, 4, and 5 (but not in Experiment 2). Overall, these results suggest that trained safety signals can reinforce avoidance behavior in humans.","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"38 1","pages":""},"PeriodicalIF":2.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142218465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Connecting self-report and instrumental behavior during incubation of food craving in humans.","authors":"Nicholas A Ruiz, Devlin Eckardt, Lisa A Briand, Mathieu Wimmer, Vishnu P Murty","doi":"10.1101/lm.053869.123","DOIUrl":"10.1101/lm.053869.123","url":null,"abstract":"<p><p>Incubation of craving is a phenomenon describing the intensification of craving for a reward over extended periods of abstinence from reinforcement. Animal models use instrumental markers of craving to reward cues to examine incubation, while human paradigms rely on subjective self-reports. Here, we characterize an animal-inspired, novel human paradigm that showed strong positive relationships between self-reports and instrumental markers of craving for favored palatable foods. Further, we found consistent nonlinear relationships with time since last consumption and self-reports, and preliminary patterns between time and instrumental responses. These findings provide a novel approach to establishing an animal-inspired human model of incubation.</p>","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"31 7","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141860192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Network motifs exhibiting a differential response to spaced and massed inputs.","authors":"Ashley Sreejan, Priyanka Saxena, Chetan J Gadgil","doi":"10.1101/lm.054012.124","DOIUrl":"10.1101/lm.054012.124","url":null,"abstract":"<p><p>One characteristic of long-term memory is the existence of an inverted U-shaped response to increasing intervals between training sessions, and consequently, an optimal spacing that maximizes memory formation. Current models of this spacing effect focus on specific molecular components and their interactions. Here, we computationally study the underlying network architecture, in particular, the potential of motif dynamics in qualitatively capturing the spacing effect in a manner that is independent of the animal model, biomolecular components, and the timescales involved. We define a common training and test protocol, and computationally identify network topologies that can qualitatively replicate the experimentally observed characteristics of the spacing effect. For 41 motifs derived from fundamental network architectures such as autoregulation, feedback, and feedforward motifs, we tested their capacity to manifest the spacing effect in terms of an inverted U-shaped response curve, using different combinations of stimulation protocols, response metrics, and kinetic parameters. Our findings indicate that positive feedback motifs where the stimulus enhances conversion reaction in the loop replicate the spacing effect across all response metrics, while feedforward motifs exhibit a metric-specific spacing effect. For some parameter combinations, linear cascades of activation and conversion reactions were found sufficient to qualitatively exhibit spacing effect characteristics.</p>","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"31 7","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792852","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flexible decision-making is related to strategy learning, vicarious trial and error, and medial prefrontal rhythms during spatial set-shifting.","authors":"Jesse T Miles, Ginger L Mullins, Sheri J Y Mizumori","doi":"10.1101/lm.053911.123","DOIUrl":"10.1101/lm.053911.123","url":null,"abstract":"<p><p>Flexible decision-making requires a balance between exploring features of an environment and exploiting prior knowledge. Behavioral flexibility is typically measured by how long it takes subjects to consistently make accurate choices after reward contingencies switch or task rules change. This measure, however, only allows for tracking flexibility across multiple trials, and does not assess the degree of flexibility. Plus, although increases in decision-making accuracy are strong indicators of learning, other decision-making behaviors have also been suggested as markers of flexibility, such as the on-the-fly decision reversals known as vicarious trial and error (VTE) or switches to a different, but incorrect, strategy. We sought to relate flexibility, learning, and neural activity by comparing choice history-derived evaluation of strategy use with changes in decision-making accuracy and VTE behavior while recording from the medial prefrontal cortex (mPFC) in rats. Using a set-shifting task that required rats to repeatedly switch between spatial decision-making strategies, we show that a previously developed strategy likelihood estimation procedure could identify putative learning points based on decision history. We confirm the efficacy of learning point estimation by showing increases in decision-making accuracy aligned to the learning point. Additionally, we show increases in the rate of VTE behavior surrounding identified learning points. By calculating changes in strategy likelihoods across trials, we tracked flexibility on a trial-by-trial basis and show that flexibility scores also increased around learning points. Further, we demonstrate that VTE behaviors could be separated into indecisive and deliberative subtypes depending on whether they occurred during periods of high or low flexibility and whether they led to correct or incorrect choice outcomes. Field potential recordings from the mPFC during decisions exhibited increased beta band activity on trials with VTE compared to non-VTE trials, as well as increased gamma during periods when learned strategies could be exploited compared to prelearning, exploratory periods. This study demonstrates that increased behavioral flexibility and VTE rates are often aligned to task learning. These relationships can break down, however, suggesting that VTE is not always an indicator of deliberative decision-making. Additionally, we further implicate the mPFC in decision-making and learning by showing increased beta-based activity on VTE trials and increased gamma after learning.</p>","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"31 7","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748518","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient enhancement of stimulus-evoked activity in neocortex during sensory learning.","authors":"Mo Zhu, Sandra J Kuhlman, Alison L Barth","doi":"10.1101/lm.053870.123","DOIUrl":"10.1101/lm.053870.123","url":null,"abstract":"<p><p>Synaptic potentiation has been linked to learning in sensory cortex, but the connection between this potentiation and increased sensory-evoked neural activity is not clear. Here, we used longitudinal in vivo Ca²⁺ imaging in the barrel cortex of awake mice to test the hypothesis that increased excitatory synaptic strength during the learning of a whisker-dependent sensory-association task would be correlated with enhanced stimulus-evoked firing. To isolate stimulus-evoked responses from dynamic, task-related activity, imaging was performed outside of the training context. Although prior studies indicate that multiwhisker stimuli drive robust subthreshold activity, we observed sparse activation of L2/3 pyramidal (Pyr) neurons in both control and trained mice. Despite evidence for excitatory synaptic strengthening at thalamocortical and intracortical synapses in this brain area at the onset of learning-indeed, under our imaging conditions thalamocortical axons were robustly activated-we observed that L2/3 Pyr neurons in somatosensory (barrel) cortex displayed only modest increases in stimulus-evoked activity that were concentrated at the onset of training. Activity renormalized over longer training periods. In contrast, when stimuli and rewards were uncoupled in a pseudotraining paradigm, stimulus-evoked activity in L2/3 Pyr neurons was significantly suppressed. These findings indicate that sensory-association training but not sensory stimulation without coupled rewards may briefly enhance sensory-evoked activity, a phenomenon that might help link sensory input to behavioral outcomes at the onset of learning.</p>","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"31 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11261211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated stimulation of feeding mechanoafferents in <i>Aplysia</i> generates responses consistent with the release of food.","authors":"Itay Hurwitz, Shlomit Tam, Jian Jing, Hillel J Chiel, Abraham J Susswein","doi":"10.1101/lm.053880.123","DOIUrl":"10.1101/lm.053880.123","url":null,"abstract":"<p><p>How does repeated stimulation of mechanoafferents affect feeding motor neurons? Monosynaptic connections from a mechanoafferent population in the <i>Aplysia</i> buccal ganglia to five motor followers with different functions were examined during repeated stimulus trains. The mechanoafferents produced both fast and slow synaptic outputs, which could be excitatory or inhibitory. In contrast, other <i>Aplysia</i> mechanoafferents produce only fast excitation on their followers. In addition, patterns of synaptic connections were different to the different motor followers. Some followers received both fast excitation and fast inhibition, whereas others received exclusively fast excitation. All followers showed strong decreases in fast postsynaptic potential (PSP) amplitude within a stimulus train. Fast and slow synaptic connections were of net opposite signs in some followers but not in others. For one follower, synaptic contacts were not uniform from all subareas of the mechanoafferent cluster. Differences in properties of the buccal ganglia mechanoafferents and other <i>Aplysia</i> mechanoafferents may arise because the buccal ganglia neurons innervate the interior of the feeding apparatus, rather than an external surface, and connect to motor neurons for muscles with different motor functions. Fast connection patterns suggest that these synapses may be activated when food slips, biasing the musculature to release food. The largest slow inhibitory synaptic PSPs may contribute to a delay in the onset of the next behavior. Additional functions are also possible.</p>","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"31 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11261209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple changes in connectivity between buccal ganglia mechanoafferents and motor neurons with different functions after learning that food is inedible in <i>Aplysia</i>.","authors":"Itay Hurwitz, Shlomit Tam, Jian Jing, Hillel J Chiel, Jeffrey Gill, Abraham J Susswein","doi":"10.1101/lm.053882.123","DOIUrl":"10.1101/lm.053882.123","url":null,"abstract":"<p><p>Changes caused by learning that a food is inedible in <i>Aplysia</i> were examined for fast and slow synaptic connections from the buccal ganglia S1 cluster of mechanoafferents to five followers, in response to repeated stimulus trains. Learning affected only fast connections. For these, unique patterns of change were present in each follower, indicating that learning differentially affects the different branches of the mechanoafferents to their followers. In some followers, there were increases in either excitatory or inhibitory connections, and in others, there were decreases. Changes in connectivity resulted from changes in the amplitude of excitation or inhibition, or as a result of the number of connections, or of both. Some followers also exhibited changes in either within or between stimulus train plasticity as a result of learning. In one follower, changes differed from the different areas of the S1 cluster. The patterns of changes in connectivity were consistent with the behavioral changes produced by learning, in that they would produce an increase in the bias to reject or to release food, and a decrease in the likelihood to respond to food.</p>","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"31 6","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11261210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141476910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrative sensor of body states: how the mushroom body modulates behavior depending on physiological context.","authors":"Raquel Suárez-Grimalt, Ilona C Grunwald Kadow, Lisa Scheunemann","doi":"10.1101/lm.053918.124","DOIUrl":"10.1101/lm.053918.124","url":null,"abstract":"<p><p>The brain constantly compares past and present experiences to predict the future, thereby enabling instantaneous and future behavioral adjustments. Integration of external information with the animal's current internal needs and behavioral state represents a key challenge of the nervous system. Recent advancements in dissecting the function of the <i>Drosophila</i> mushroom body (MB) at the single-cell level have uncovered its three-layered logic and parallel systems conveying positive and negative values during associative learning. This review explores a lesser-known role of the MB in detecting and integrating body states such as hunger, thirst, and sleep, ultimately modulating motivation and sensory-driven decisions based on the physiological state of the fly. State-dependent signals predominantly affect the activity of modulatory MB input neurons (dopaminergic, serotoninergic, and octopaminergic), but also induce plastic changes directly at the level of the MB intrinsic and output neurons. Thus, the MB emerges as a tightly regulated relay station in the insect brain, orchestrating neuroadaptations due to current internal and behavioral states leading to short- but also long-lasting changes in behavior. While these adaptations are crucial to ensure fitness and survival, recent findings also underscore how circuit motifs in the MB may reflect fundamental design principles that contribute to maladaptive behaviors such as addiction or depression-like symptoms.</p>","PeriodicalId":18003,"journal":{"name":"Learning & memory","volume":"31 5","pages":""},"PeriodicalIF":1.8,"publicationDate":"2024-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11199956/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141321141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}