{"title":"The brain works at more than 10 bits per second","authors":"Britton A. Sauerbrei, J. Andrew Pruszynski","doi":"10.1038/s41593-025-01997-0","DOIUrl":"https://doi.org/10.1038/s41593-025-01997-0","url":null,"abstract":"A recent article makes a claim with far-reaching implications for neuroscience, technology, and society: that the human brain is subject to an information processing ‘speed limit’ of 10 bits per second. Although this speed limit appears to hold for high-level cognitive functions, we argue that unconscious processing for real-time control of movement, which occupies a majority of neurons in the central nervous system and accounts for most of the information throughput of humans, substantially exceeds this limit.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"22 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144279001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pablo Gimenez-Gomez, Timmy Le, Max Zinter, Peter M’Angale, Violeta Duran-Laforet, Timothy G. Freels, Rebecca Pavchinskiy, Susanna Molas, Dorothy P. Schafer, Andrew R. Tapper, Travis Thomson, Gilles E. Martin
{"title":"Suppression of binge alcohol drinking by an inhibitory neuronal ensemble in the mouse medial orbitofrontal cortex","authors":"Pablo Gimenez-Gomez, Timmy Le, Max Zinter, Peter M’Angale, Violeta Duran-Laforet, Timothy G. Freels, Rebecca Pavchinskiy, Susanna Molas, Dorothy P. Schafer, Andrew R. Tapper, Travis Thomson, Gilles E. Martin","doi":"10.1038/s41593-025-01970-x","DOIUrl":"https://doi.org/10.1038/s41593-025-01970-x","url":null,"abstract":"<p>Alcohol consumption remains a significant global health challenge, directly and indirectly causing millions of deaths annually. Alcohol abuse causes dysregulated activity of the prefrontal cortex, yet effects on specific prefrontal circuits remain to be elucidated. Here, we identify a discrete GABAergic neuronal ensemble in the mouse medial orbitofrontal cortex (mOFC) that is selectively recruited in response to binge alcohol drinking and limits further drinking behavior. Optogenetic silencing of this population, or its ablation, results in uncontrolled binge alcohol consumption. This neuronal ensemble is specific to alcohol and is not recruited by other rewarding substances. Neurons in this ensemble project widely throughout the brain, but projections specifically to the mediodorsal thalamus regulate binge alcohol drinking. Together, these results identify a brain circuit in the mOFC that serves to protect against binge drinking by reducing alcohol intake, which may offer avenues for the development of mOFC neuronal ensemble-targeted interventions.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"21 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Benjamin A. Plog, Kyungdeok Kim, Daan Verhaege, Min Woo Kim, Zachary Papadopoulos, Krikor Dikranian, Taitea Dykstra, Jay Cao, Richard J. Perrin, Katherine E. Schwetye, Jonathan Kipnis, Antoine Drieu
{"title":"A route for cerebrospinal fluid flow through leptomeningeal arterial–venous overlaps enables macromolecule and fluid shunting","authors":"Benjamin A. Plog, Kyungdeok Kim, Daan Verhaege, Min Woo Kim, Zachary Papadopoulos, Krikor Dikranian, Taitea Dykstra, Jay Cao, Richard J. Perrin, Katherine E. Schwetye, Jonathan Kipnis, Antoine Drieu","doi":"10.1038/s41593-025-01977-4","DOIUrl":"https://doi.org/10.1038/s41593-025-01977-4","url":null,"abstract":"<p>The flow of cerebrospinal fluid (CSF) is important for conveying brain-derived macromolecules for signaling and enabling them to be drained from the brain parenchyma. The glymphatic route is the best-characterized means of this CSF flow; however, it does not permit the movement of larger macromolecules. Here, we identify in mice an alternative route whereby intra-CSF-injected macromolecules can traverse from periarterial to perivenous spaces, with transfer occurring at sites of overlap between leptomeningeal perivascular (arteriovenous) spaces dispersed across the surface of the brain’s leptomeninges. We show that intra-CSF-injected fluorescent tracers can reach the perivenous space by passing through these arteriovenous perivascular overlaps. These spaces remain functional in a mouse model of amyloidosis and are essential for clearing excess CSF volume. These anatomical structures may support brain function by allowing the drainage of brain-derived macromolecules and the shunting of excess fluid and by aiding the immune surveillance of freshly generated CSF.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"10 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jakob Voigts, Ingmar Kanitscheider, Nicholas J. Miller, Enrique H. S. Toloza, Jonathan P. Newman, Ila R. Fiete, Mark T. Harnett
{"title":"Spatial reasoning via recurrent neural dynamics in mouse retrosplenial cortex","authors":"Jakob Voigts, Ingmar Kanitscheider, Nicholas J. Miller, Enrique H. S. Toloza, Jonathan P. Newman, Ila R. Fiete, Mark T. Harnett","doi":"10.1038/s41593-025-01944-z","DOIUrl":"https://doi.org/10.1038/s41593-025-01944-z","url":null,"abstract":"<p>From visual perception to language, sensory stimuli change their meaning depending on previous experience. Recurrent neural dynamics can interpret stimuli based on externally cued context, but it is unknown whether they can compute and employ internal hypotheses to resolve ambiguities. Here we show that mouse retrosplenial cortex (RSC) can form several hypotheses over time and perform spatial reasoning through recurrent dynamics. In our task, mice navigated using ambiguous landmarks that are identified through their mutual spatial relationship, requiring sequential refinement of hypotheses. Neurons in RSC and in artificial neural networks encoded mixtures of hypotheses, location and sensory information, and were constrained by robust low-dimensional dynamics. RSC encoded hypotheses as locations in activity space with divergent trajectories for identical sensory inputs, enabling their correct interpretation. Our results indicate that interactions between internal hypotheses and external sensory data in recurrent circuits can provide a substrate for complex sequential cognitive reasoning.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"9 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144228854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Sleep cycles process memories","authors":"William P. Olson","doi":"10.1038/s41593-025-01996-1","DOIUrl":"https://doi.org/10.1038/s41593-025-01996-1","url":null,"abstract":"<p>Memory replay during sleep probably facilitates the transfer of memories from intermediate storage in the hippocampus to long-term storage in the cortex. In a paper published in <i>Neuron</i>, Bollmann, Baracskay et al. reveal that memories are not static during this process, but are instead transformed into their long-term state during the sleep period. The authors tracked spatial memory ensembles in the hippocampus of rats across acquisition, a prolonged (17–20 h) sleep/rest period and recall the following day. Acquisition and recall induced distinct neuronal ensembles, and ensemble activity gradually evolved from an acquisition-like to a recall-like state during sleep. Interestingly, non-REM sleep pushed memory drift towards recall, whereas REM sleep counteracted this drift. These findings echo prior work that indicated a crucial role for non-REM sleep in consolidation and also offer intriguing clues regarding the potentially distinct roles of non-REM and REM sleep in this process.</p><p><b>Original reference:</b> <i>Neuron</i> https://doi.org/10.1016/j.neuron.2025.02.025 (2025)</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"39 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144236945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tuning arousal","authors":"Laura Zelenka","doi":"10.1038/s41593-025-01994-3","DOIUrl":"https://doi.org/10.1038/s41593-025-01994-3","url":null,"abstract":"<p>The locus coeruleus (LC), a major source of noradrenaline in the brain, plays a crucial role in regulating arousal and behavior. Despite its known functions, the mechanisms that control LC activity, particularly the influence of local GABAergic (γ-aminobutyric acid-producing) neurons, remain poorly understood. In a study published in <i>Nature</i>, Luskin, Li et al. identified a heterogeneous population of peri-LC<sup>GABA</sup> neurons that directly inhibit LC neurons, thereby modulating arousal and avoidance behaviors. Using optogenetic and chemogenetic approaches in mice, the authors demonstrated that activation of peri-LC<sup>GABA</sup> neurons markedly suppresses arousal and exploration, whereas inhibiting them heightens anxiety-like and avoidance behaviors. They further revealed the molecular diversity of neuronal populations within both the peri-LC and LC regions by using single-nucleus and spatial transcriptomic analyses in behaving mice. Subsequent experiments uncovered distinct neural responses to various stimuli in specific neuropeptide-expressing subpopulations and implicated these subpopulations in modulating arousal and avoidance behaviors. Together, these findings highlight peri-LC<sup>GABA</sup> neurons as key regulators of LC activity, linking them to arousal-related behaviors and suggesting potential therapeutic targets for neuropsychiatric disorders.</p><p><b>Original reference:</b> <i>Nature</i> https://doi.org/10.1038/s41586-025-08952-w (2025)</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"10 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dopamine says do that again","authors":"Luis A. Mejia","doi":"10.1038/s41593-025-01995-2","DOIUrl":"https://doi.org/10.1038/s41593-025-01995-2","url":null,"abstract":"<p>Repeated actions may be reinforced through action prediction error — the difference between an executed action and its prediction given a particular state — but experimental evidence for such a movement-based, value-free teaching signal has been lacking. Greenstreet, Martinez Vergara, Johansson et al. trained mice on an auditory discrimination task and found that dopamine in the tail of the striatum (TS) is needed for learning, and that TS dopamine levels correlate with movement, but not reward, on the choice task. The movement-related dopamine signal in TS decreased over the course of learning, increased when an unfamiliar stimulus was used, and reinforced stimulus–action associations on the choice task; these findings are consistent with dopamine encoding a value-free action prediction error. A dual-controller model incorporating both value-based (reward prediction error via ventral striatum) and value-free (action prediction error via TS) systems learned the task faster than a value-based controller alone and implicated a role for TS during the later stages of learning. These findings suggest that movement-related dopamine signals in TS, and perhaps in other parts of the dorsal striatum, encode a value-free teaching signal that reinforces state–action associations, promoting the repetition of actions. Action prediction error may thus serve as the basis for the implementation of habitual behavior.</p><p><b>Original reference:</b> <i>Nature</i> https://doi.org/10.1038/s41586-025-09008-9 (2025)</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"523 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kyoko Tossell, Xiao Yu, Panagiotis Giannos, Berta Anuncibay Soto, Mathieu Nollet, Raquel Yustos, Giulia Miracca, Mikal Vicente, Andawei Miao, Bryan Hsieh, Ying Ma, Alexei L. Vyssotski, Tim Constandinou, Nicholas P. Franks, William Wisden
{"title":"Author Correction: Somatostatin neurons in prefrontal cortex initiate sleep-preparatory behavior and sleep via the preoptic and lateral hypothalamus","authors":"Kyoko Tossell, Xiao Yu, Panagiotis Giannos, Berta Anuncibay Soto, Mathieu Nollet, Raquel Yustos, Giulia Miracca, Mikal Vicente, Andawei Miao, Bryan Hsieh, Ying Ma, Alexei L. Vyssotski, Tim Constandinou, Nicholas P. Franks, William Wisden","doi":"10.1038/s41593-025-02003-3","DOIUrl":"https://doi.org/10.1038/s41593-025-02003-3","url":null,"abstract":"<p>Correction to: <i>Nature Neuroscience</i> https://doi.org/10.1038/s41593-023-01430-4, published online 21 September 2023.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"25 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"RNA dysregulation impairs stress resilience in aged neurons","authors":"","doi":"10.1038/s41593-025-01953-y","DOIUrl":"https://doi.org/10.1038/s41593-025-01953-y","url":null,"abstract":"Aging is a primary risk factor for neurodegenerative diseases. This study shows that key RNA pathways are disrupted in old neurons, including splicing and the stress response. Because of these changes, the aging brain has reduced resilience to new stress, which might predispose old neurons to disease.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"45 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144218884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Takahiro Noda, Eike Kienle, Jens-Bastian Eppler, Dominik F. Aschauer, Matthias Kaschube, Yonatan Loewenstein, Simon Rumpel
{"title":"Homeostasis of a representational map in the neocortex","authors":"Takahiro Noda, Eike Kienle, Jens-Bastian Eppler, Dominik F. Aschauer, Matthias Kaschube, Yonatan Loewenstein, Simon Rumpel","doi":"10.1038/s41593-025-01982-7","DOIUrl":"https://doi.org/10.1038/s41593-025-01982-7","url":null,"abstract":"<p>Cortical function, including sensory processing, is surprisingly resilient to neuron loss during aging and neurodegeneration. In this Article, we used the mouse auditory cortex to investigate how homeostatic mechanisms protect the representational map of sounds after neuron loss. We combined two-photon calcium imaging with targeted microablation of 30–40 sound-responsive neurons in layer 2/3. Microablation led to a temporary disturbance of the representational map, but it recovered in the following days. Recovery was primarily driven by neurons that were initially unresponsive to sounds but gained responsiveness and strengthened the network’s correlation structure. By contrast, selective microablation of inhibitory neurons caused prolonged disturbance, characterized by destabilized sound responses. Our results link individual neuron tuning and plasticity to the stability of the population-level representational map, highlighting homeostatic mechanisms that safeguard sensory processing in the neocortex.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"102 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144219037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}