Jasmin A. Strickland , Joseph M. Austen , Rolf Sprengel , David J. Sanderson
{"title":"The GRIA1 AMPA receptor subunit and selective learning","authors":"Jasmin A. Strickland , Joseph M. Austen , Rolf Sprengel , David J. Sanderson","doi":"10.1016/j.nlm.2025.108089","DOIUrl":"10.1016/j.nlm.2025.108089","url":null,"abstract":"<div><div>The GRIA1 subunit of the AMPA receptor, encoded by the <em>GRIA1</em> gene, has been implicated in schizophrenia. Schizophrenia is associated with impairments in attention that may lead to other symptoms due to a failure to learn selectively (e.g., learning about redundant cues). In mice, gene-targeted inactivation of <em>GRIA1</em> impairs hippocampal synaptic plasticity and alters learning and memory. To test the role of GRIA1 in selective learning, we trained mice lacking <em>GRIA1</em> on the blocking procedure. <em>GRIA1</em> knockout mice showed normal blocking of appetitive Pavlovian conditioning, in which prior learning of an auditory cue reduced subsequent acquisition of conditioned responding to a visual cue when the two cues were trained in compound. <em>GRIA1</em> knockout mice, however, failed to show blocking of flavour preference conditioning despite normal learning of the flavour that, in contrast, was effective in blocking conditioning in control mice. This impairment occurred under conditions in which mice were exposed to one flavour a day and when exposed to two flavours a day to aid discrimination between flavours. The dissociation between learning with visual cues and learning with flavours may suggest that GRIA1 containing AMPA receptors are necessary for selective learning for particular stimulus modalities. Alternatively, GRIA1 may play a role in selective learning when the similarity between cues competing for learning is high, as for flavour preference learning, but not when low, as for auditory and visual cues.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108089"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874287","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}
J.R. Watson, M.D. Lopez de Leon, E.L. Carlson, P.J. Vento
{"title":"Long-lasting avoidance induced by repeated stimulation of the rostromedial tegmental nucleus","authors":"J.R. Watson, M.D. Lopez de Leon, E.L. Carlson, P.J. Vento","doi":"10.1016/j.nlm.2025.108111","DOIUrl":"10.1016/j.nlm.2025.108111","url":null,"abstract":"<div><div>Adaptive decision-making requires the ability to weigh the relative costs versus the benefits of our actions and to flexibly respond to changing environmental contingencies. While midbrain dopamine (DA) has been a major focus of study for its role in associative learning, motivation, and reward seeking, far less is known regarding the contribution of inhibitory dopamine inputs in promoting behavioral inhibition and avoidance learning. The rostromedial tegmental nucleus (RMTg) sends dense GABAergic projections to DA neurons in the ventral tegmental area (VTA) and mounting evidence suggests the RMTg–VTA circuit is required to suppress reward seeking under punishment, but it remains unclear whether stimulation of this pathway is sufficient to drive learning and promote shifts in cost-benefit decisions. To test this, we developed two separate tasks of passive and active avoidance in rats where lever pressing for food reward was associated with repeated stimulation of the RMTg–VTA circuit. In a one-lever fixed ratio 5 food-seeking task, we found that pairing contingent RMTg–VTA stimulation immediately after responding for reward delivery caused a robust, yet transient suppression of reward seeking that quickly returned to baseline after stimulation ceased. When given an alternative reward choice, however, RMTg–VTA stimulation caused a rapid and enduring shift in subjective choice leading to persistent and selective avoidance of the stimulation-paired reward. These findings support a multifaceted role for the RMTg–VTA pathway in learning and decision-making and provide key insights into the neural mechanisms underlying behavioral avoidance and cost-benefit decisions.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108111"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145409676","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":"Analysis of neural plasticity genes’ expression in fish brain reveals the basis of individual differences in learning","authors":"Elia Gatto , Elisa Samorì , Elena Frigato , Cristiano Bertolucci , Tyrone Lucon-Xiccato","doi":"10.1016/j.nlm.2025.108106","DOIUrl":"10.1016/j.nlm.2025.108106","url":null,"abstract":"<div><div>Individual differences in cognition have been historically recognized in humans, and recent evidence suggests that such variation is widespread across the animal kingdom. Despite its importance for individuals’ behaviour and fitness, the biological roots of cognitive variation remain poorly understood. We hypothesize that variation in brain gene expression is important in determining individual cognitive differences. To test this, we focused on 6 neural plasticity genes and examined fish, which exhibit the largest cognitive variation reported for vertebrates. Zebrafish (<em>Danio rerio</em>) exposed to visual discrimination tasks showed substantial variation in their performance, with some learning over 7 times faster than others. Expression of two genes positively predicted learning performance. However, expression levels of most genes were related at the individual level, suggesting that multi-gene expression patterns may be more relevant than single gene variation. Principal component analysis identified two axes of multi-gene expression variation: the first loaded by all genes except neurotrophin <em>bdnf</em>, the second mainly loaded by <em>bdnf</em> and <em>neurod1</em> expression. Only the latter component significantly predicted learning performance in a visual discrimination task, indicating that individual variation in <em>bdnf</em> expression and with lesser extend <em>neurod1</em> are critical for learning. Our study bridges the gap between cognitive differences and molecular mechanisms underlying brain function, providing foundation for new understanding what makes individual unique.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108106"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280874","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":"Towards a multi-dimensional understanding of brain states","authors":"Tomomi Karigo , Adam S. Charles","doi":"10.1016/j.nlm.2025.108110","DOIUrl":"10.1016/j.nlm.2025.108110","url":null,"abstract":"<div><div>Animals continuously adapt their behaviors to navigate diverse and dynamic environments effectively. Such behavioral flexibility emerges from internal states that modulate responses to environmental stimuli. Traditionally, these states have been studied individually and treated as discrete, categorical variables. However, recent advances in neural recording and behavioral analyses now enable quantitative extraction of states directly from data, and emerging evidence indicates that animals simultaneously experience multiple, often interacting, internal states that dynamically modulate neural activity and behavior. In this review, we propose a multi-dimensional framework for understanding brain states as modulators that influence the relationship between the environment, neural activity, and behavior. We highlight recent neurobiological studies demonstrating how interacting physiological and emotional states, such as hunger and aggression, can reconfigure behavior through circuit-level integration. Additionally, we discuss evidence from large-scale neural recordings showing distributed and graded representations of internal states across the brain. Computational models, particularly those utilizing unsupervised clustering and dynamical systems, further enable the investigation of these flexible, context-dependent state interactions. Finally, we propose further integration of high-resolution brain-wide recording and computational modeling approaches to understand how multiple internal states integrate to shape neural coding and behavior. Such integrative approaches are critical for uncovering the neural mechanisms underlying flexible and adaptive behaviors in naturalistic settings.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108110"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416887","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":"Mechanisms for punishment learning and decision-making: A special issue","authors":"Philip Jean-Richard-dit-Bressel","doi":"10.1016/j.nlm.2025.108108","DOIUrl":"10.1016/j.nlm.2025.108108","url":null,"abstract":"","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108108"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145329705","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}
Jake R. Embrey , Kelly G. Garner , Julyani Salim , Poppy Watson
{"title":"Modelling Pavlovian biases in depressed and healthy young adults","authors":"Jake R. Embrey , Kelly G. Garner , Julyani Salim , Poppy Watson","doi":"10.1016/j.nlm.2025.108092","DOIUrl":"10.1016/j.nlm.2025.108092","url":null,"abstract":"<div><div>Pavlovian stimuli signalling potential punishment and reward have powerful effects on instrumental behaviours. For example, a cue associated with punishment will suppress well-learned instrumental responses. However, the degree to which Pavlovian stimuli interfere with the <em>learning</em> of instrumental responses is less well studied. In the current set of studies we investigated the effect of Pavlovian stimuli on instrumental learning and the extent to which depressive symptomatology moderated this relationship. We conducted two experiments using a sample of healthy adults and leveraged computational modelling to estimate learning parameters and the moderating role of depression on these learning parameters. In line with previous literature, participants found it more difficult to learn to make instrumental go and no-go responses in the presence of incongruent cues—for instance, making a “go” response for a cue which signalled punishment, and vice versa. Contrary to expectation we did not observe a reliable relationship between performance and depression scores; while Experiment 1 observed a relationship between depression and model-derived learning rates, these results were not replicated in Experiment 2. We discuss both the theoretical and practical implications of these findings in the General Discussion.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108092"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030284","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}
Krista A. Mitchnick , Samantha D. Creighton , Karanveer S. Johal , Sanya Anoop , Bettina E. Kalisch , Gilda Stefanelli , Boyer D. Winters
{"title":"Double dissociation between the involvement of Gadd45α and Gadd45β/γ in the perirhinal cortex and hippocampus of male rats for object memory","authors":"Krista A. Mitchnick , Samantha D. Creighton , Karanveer S. Johal , Sanya Anoop , Bettina E. Kalisch , Gilda Stefanelli , Boyer D. Winters","doi":"10.1016/j.nlm.2025.108113","DOIUrl":"10.1016/j.nlm.2025.108113","url":null,"abstract":"<div><div>The GADD45 family of proteins (GADD45α, GADD45β, GADD45γ) has been implicated in DNA demethylation and long-term memory formation. Recently, conflicting findings have emerged surrounding the involvement of Gadd45α in various object recognition tasks. These discrepancies could be due to differences in Gadd45α KO mouse models and/or task parameters. Further, the use of brain-wide KO models precludes our understanding of Gadd45α in specific brain regions such as the hippocampus (HPC), which processes the spatial location of objects, or the perirhinal cortex (PRh), which has a larger role in object identity memory. Here, using a single object recognition task reliant on both the PRh and HPC – the object-in-place (OiP) task – we show that siRNA knockdown of <em>Gadd45β</em> or <em>Gadd45γ,</em> but not <em>Gadd45α,</em> within the dorsal HPC (dHPC) impaired long-term, but not short-term, OiP memory. Further, OiP learning induced an upregulation of <em>Gadd45β</em> mRNA in the dentate gyrus subregion of the dHPC. Within the PRh, siRNA knockdown of <em>Gadd45α,</em> but not <em>Gadd45β</em> or <em>Gadd45γ,</em> impaired long-term, but not short-term, OiP memory, with a concomitant increase in learning induced PRh <em>Gadd45α</em> mRNA. These results clarify previous discrepancies in the literature by demonstrating a clear necessity for Gadd45α in the PRh, but not the dHPC, for the consolidation of long-term object memories.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108113"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145445513","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":"Are the principles of Pavlovian conditioning in insects conserved with those in mammals?","authors":"Makoto Mizunami","doi":"10.1016/j.nlm.2025.108104","DOIUrl":"10.1016/j.nlm.2025.108104","url":null,"abstract":"<div><div>Pavlovian conditioning, in which a relatively insignificant stimulus (the conditioned stimulus, CS) is paired with a biologically significant stimulus (the unconditioned stimulus, US), is a ubiquitous form of associative learning found in many animal phyla. Modern theories in mammals suggest that the prediction error, i.e., the discrepancy between the predicted unconditioned stimulus (US) and the actual US, drives conditioning, and that the conditioned response (CR) to the conditioned stimulus (CS) is flexibly guided by the expectation of the US. These theories were proposed to overcome limitations of conventional theories, which assume that contingency or correlation between the CS and US is sufficient to account for the achievement of conditioning and that the strength of the CS-US association is enough to determine the magnitude of the CR. It remained unclear, however, whether the modern theories account for Pavlovian conditioning in invertebrates. Here, I address this issue by reviewing recent studies in insects. It has been demonstrated that the error correction learning rule achieves the conditioning in crickets, and the production of the CR is guided by the current value of the US in fruit flies, crickets, and honey bees. From these findings, I conclude that the principles of Pavlovian conditioning in insects are, in essence, conserved with those in mammals. A crucial question to be addressed is how sophisticated forms of Pavlovian conditioning, comparable to those achieved in large-scale neural networks in mammalian brains, are accomplished by small-scale neural networks in insects.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108104"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150192","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}
Abigail Yap Flores, Nolee V. Bugarin, Adolfo Torres, Adeline Cheng, Pascale Fung, Donya Mohammadi, Madeline F. Winters, Gyorgy Lur
{"title":"Adolescent stress exposure induces persistent, sex-specific cognitive deficits","authors":"Abigail Yap Flores, Nolee V. Bugarin, Adolfo Torres, Adeline Cheng, Pascale Fung, Donya Mohammadi, Madeline F. Winters, Gyorgy Lur","doi":"10.1016/j.nlm.2025.108103","DOIUrl":"10.1016/j.nlm.2025.108103","url":null,"abstract":"<div><div>Exposure to stress or adversity during adolescence has been shown to produce both short-term and long-lasting effects on cognitive functions. Diminished learning and memory, reduced attention, and impaired decision making in adulthood are some of the most prevalent consequences of experiencing severe adversity during childhood. In addition, numerous long-term effects of stress have been shown to be sex dependent. Yet, longitudinal studies that comprehensively assess the lasting cognitive effects of adolescent stress in both sexes remain scarce. Here, we exposed male and female mice to multiple concurrent stressors repeated over ten days during early- to mid-adolescence. After reaching adulthood, mice were trained in a sensory discrimination task, where we measured learning rates, delayed response performance, and sensitivity to distractors. We found a significant reduction of learning speed in stressed female mice, but not in males. In contrast, stressed males showed weaker delayed discrimination performance and substantial sensitivity to distractors. Our data indicates that these effects may be driven by increased propensity to respond, rather than reduced sensory sensitivity. Overall, we found marked sex differences in the long-term cognitive effects of adolescent exposure to stress.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108103"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046393","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}
Siri-Maria Kamp , Luisa Knopf , Meike Kroneisen , Edgar Erdfelder
{"title":"Event-related potentials uncover the neurocognitive encoding and retrieval mechanisms of animacy effects in episodic memory","authors":"Siri-Maria Kamp , Luisa Knopf , Meike Kroneisen , Edgar Erdfelder","doi":"10.1016/j.nlm.2025.108112","DOIUrl":"10.1016/j.nlm.2025.108112","url":null,"abstract":"<div><div>Episodic memory performance is consistently higher for animate stimuli like humans or animals than for inanimate objects. To examine the mechanisms underlying this “animacy effect”, we recorded event-related potentials (ERPs) while healthy, young adults encoded and subsequently freely recalled (Experiment 1) or recognized (Experiment 2) words referring to animate and inanimate objects. In both experiments, we replicated the animacy effect. Further, in both experiments, animates elicited smaller N400-amplitudes than inanimates during encoding, suggesting that semantic access is facilitated for animate stimuli. No differences were found between stimulus types in any ERP markers thought to index elaborative encoding. In Experiment 2, the word types did not differ in the early mid-frontal and the left parietal old/new effects during recognition, indexing familiarity and bottom-up recollection, respectively. However, the late posterior negativity, presumably indexing controlled, effortful reconstruction of the study episode, was prominent for animates but absent for inanimates. Taken together, these results support a difference in the semantic representation between animates and inanimates, and more effortful recollection of a more complex episodic memory trace of animates during retrieval. Notably, these ERP patterns differ qualitatively from recent results on the survival processing effect, supporting a dissociation of the mechanisms behind the two effects.</div></div>","PeriodicalId":19102,"journal":{"name":"Neurobiology of Learning and Memory","volume":"222 ","pages":"Article 108112"},"PeriodicalIF":1.8,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416888","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}