Melanie A. Basnak, Anna Kutschireiter, Tatsuo S. Okubo, Albert Chen, Pavel Gorelik, Jan Drugowitsch, Rachel I. Wilson
{"title":"Multimodal cue integration and learning in a neural representation of head direction","authors":"Melanie A. Basnak, Anna Kutschireiter, Tatsuo S. Okubo, Albert Chen, Pavel Gorelik, Jan Drugowitsch, Rachel I. Wilson","doi":"10.1038/s41593-024-01823-z","DOIUrl":"https://doi.org/10.1038/s41593-024-01823-z","url":null,"abstract":"<p>Navigation requires us to take account of multiple spatial cues with varying levels of informativeness and learn their spatial relationships. Here we investigate this process in the <i>Drosophila</i> head direction system, which functions as a ring attractor and a topographic map of head direction. Using population calcium imaging and multimodal virtual reality environments, we show that increasing cue informativeness improves encoding accuracy and produces a narrower and higher bump of activity. When cues conflict, the more informative cue exerts more weight. A familiar cue is weighted more heavily and used to guide the remapping of a less familiar cue. When a cue is less informative, it is remapped more readily in response to cue conflict. All these results can be explained by an attractor model with plastic sensory synapses. Our findings provide a mechanistic explanation for how the brain assembles spatial representations through inference and learning.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"25 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684526","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}
Erika Atucha, Mariana Pais, Giacomo Ronzoni, Chantal Schoenmaker, Piray Atsak, David Roura, Klara J. Lohkamp, Gustav Schelling, James L. McGaugh, Jeffrey C. Glennon, Armaz Aschrafi, Benno Roozendaal
{"title":"Noradrenergic activation of the basolateral amygdala facilitates memory specificity for similar events experienced close in time","authors":"Erika Atucha, Mariana Pais, Giacomo Ronzoni, Chantal Schoenmaker, Piray Atsak, David Roura, Klara J. Lohkamp, Gustav Schelling, James L. McGaugh, Jeffrey C. Glennon, Armaz Aschrafi, Benno Roozendaal","doi":"10.1038/s41593-025-02014-0","DOIUrl":"https://doi.org/10.1038/s41593-025-02014-0","url":null,"abstract":"<p>Noradrenergic activation of the basolateral amygdala (BLA) promotes strong and lasting memories of emotionally arousing experiences. However, in our lives, we often encounter similar events that may be confused and result in emotional strengthening of incorrect associations. Here we provide evidence, in rats, that noradrenergic activation of the BLA promotes the formation of discrete memories of similar events that were experienced close in time, via a miR-134-regulated consolidation process within the dentate gyrus of the hippocampus. Targeted downregulation of miR-134 in the hippocampus was sufficient to induce memory specificity, without affecting the strength of the memory. Notably, noradrenergic activation of the BLA did not recruit this hippocampal miR-134-mediated mechanism in enhancing memory of a single event. These findings indicate that the BLA engages a qualitatively different neural mechanism on an ‘as-needed’ basis to facilitate the separation of similar memory representations, enabling the selective strengthening of correct associations into long-term memory.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"16 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684525","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":"Long-range cortical GABA neurons oppose binge drinking","authors":"JunShi Wang, Paul J. Kenny","doi":"10.1038/s41593-025-02030-0","DOIUrl":"https://doi.org/10.1038/s41593-025-02030-0","url":null,"abstract":"Binge drinking is widespread, but its underlying cellular mechanisms remain unclear. A recent study identifies a sparse ensemble of GABAergic neurons in the medial orbitofrontal cortex that is activated during binge drinking. These neurons send inhibitory projections to subcortical regions to limit alcohol intake, suggesting new strategies to reduce binge drinking and protect against alcohol use disorder.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"667 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684524","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":"How the retina keeps the precise timing needed for coherent visual perception","authors":"","doi":"10.1038/s41593-025-02012-2","DOIUrl":"https://doi.org/10.1038/s41593-025-02012-2","url":null,"abstract":"To perceive events as simultaneous despite differences in how sensory signals are generated and transmitted, the brain must preserve temporal coherence. We found that retinal ganglion cells adjust the speed with which they transmit neural signals, revealing a mechanism in the human retina to keep visual perception precisely timed.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"675 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677245","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}
Jiannis Taxidis, Blake Madruga, Karen Safaryan, Conor C. Dorian, Maxwell D. Melin, Zoë Day, Michael Z. Lin, Peyman Golshani
{"title":"Voltage imaging reveals hippocampal inhibitory dynamics shaping pyramidal memory-encoding sequences","authors":"Jiannis Taxidis, Blake Madruga, Karen Safaryan, Conor C. Dorian, Maxwell D. Melin, Zoë Day, Michael Z. Lin, Peyman Golshani","doi":"10.1038/s41593-025-02016-y","DOIUrl":"https://doi.org/10.1038/s41593-025-02016-y","url":null,"abstract":"<p>Hippocampal spiking sequences encode and link behaviorally relevant information across time. How inhibition sculpts these sequences remains unclear. We performed longitudinal voltage imaging of CA1 parvalbumin- and somatostatin-expressing interneurons in mice performing an odor-cued working memory task. Unlike pyramidal odor-specific sequences that encode odor and time throughout a delay period, interneurons encoded odor delivery, but not odor identity or delay time. Odor-triggered inhibition was exerted by stable numbers of interneurons across days, with constant cell turnover, independent of task training. At odor onset, brief spiking of parvalbumin interneurons was followed by widespread hyperpolarization and synchronized theta-paced rebound spiking across interneurons. Electrophysiology, optogenetics and calcium imaging corroborated that parvalbumin interneurons silenced most pyramidal cells during odor delivery, whereas somatostatin interneurons suppressed other interneurons. The few odor-selective pyramidal cells spiked together with interneuronal post-hyperpolarization rebound. Collectively, inhibition increases the signal-to-noise ratio of pyramidal cue representations, enabling efficient encoding of memory-relevant information.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"311 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677249","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":"Functionally diverse human insular architecture with memory-related hippocampal interactions","authors":"","doi":"10.1038/s41593-025-02035-9","DOIUrl":"https://doi.org/10.1038/s41593-025-02035-9","url":null,"abstract":"Direct and simultaneous recordings across the human brain during a memory encoding task involving emotionally valenced words revealed tightly clustered neuronal sites within the insular cortex with distinct roles — some tracked valence, whereas others predicted memory. Only memory-related insular sites, when electrically stimulated, sparked strong hippocampal responses, uncovering a specialized insula–hippocampus axis for successful memory encoding.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"202 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640356","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}
Feng Ye, Ying Chen, ThaoNguyen Hoang, Rusty L. Montgomery, Xian-hui Zhao, Hong Bu, Tom Hu, Makoto M. Taketo, Johan H. van Es, Hans Clevers, Jenny Hsieh, Rhonda Bassel-Duby, Eric N. Olson, Q. Richard Lu
{"title":"Author Correction: HDAC1 and HDAC2 regulate oligodendrocyte differentiation by disrupting the β-catenin–TCF interaction","authors":"Feng Ye, Ying Chen, ThaoNguyen Hoang, Rusty L. Montgomery, Xian-hui Zhao, Hong Bu, Tom Hu, Makoto M. Taketo, Johan H. van Es, Hans Clevers, Jenny Hsieh, Rhonda Bassel-Duby, Eric N. Olson, Q. Richard Lu","doi":"10.1038/s41593-025-02034-w","DOIUrl":"https://doi.org/10.1038/s41593-025-02034-w","url":null,"abstract":"<p>Correction to: <i>Nature Neuroscience</i> https://doi.org/10.1038/nn.2333, published online 7 June 2009.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"109 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144645631","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}
Robert I. McGeachan, Lois Keavey, Elizabeth M. Simzer, Ya Yin Chang, Jamie L. Rose, Maxwell P. Spires-Jones, Mollie Gilmore, Kristjan Holt, Soraya Meftah, Natalia Ravingerova, Cristina Scutariu, Lewis W. Taylor, Declan King, Makis Tzioras, Jane Tulloch, Sam A. Booker, Imran Liaquat, Nicole Hindley-Pollock, Bethany Geary, Colin Smith, Paul M. Brennan, Claire S. Durrant, Tara L. Spires-Jones
{"title":"Evidence for trans-synaptic propagation of oligomeric tau in human progressive supranuclear palsy","authors":"Robert I. McGeachan, Lois Keavey, Elizabeth M. Simzer, Ya Yin Chang, Jamie L. Rose, Maxwell P. Spires-Jones, Mollie Gilmore, Kristjan Holt, Soraya Meftah, Natalia Ravingerova, Cristina Scutariu, Lewis W. Taylor, Declan King, Makis Tzioras, Jane Tulloch, Sam A. Booker, Imran Liaquat, Nicole Hindley-Pollock, Bethany Geary, Colin Smith, Paul M. Brennan, Claire S. Durrant, Tara L. Spires-Jones","doi":"10.1038/s41593-025-01992-5","DOIUrl":"https://doi.org/10.1038/s41593-025-01992-5","url":null,"abstract":"<p>In the neurodegenerative disease progressive supranuclear palsy (PSP), tau pathology progresses through the brain in a stereotypical spatiotemporal pattern, and where tau pathology appears, synapses are lost. We tested the hypothesis that pathological tau contributes to synapse loss and may spread through the brain by moving from presynapses to postsynapses. Using postmortem PSP brain samples and a living human brain slice culture model, we observe pathological tau in synaptic pairs and evidence that oligomeric tau can enter live human postsynapses. Proteomics revealed increased clusterin in synapses in PSP, and super-resolution imaging showed clusterin colocalized with tau in synapses in close enough proximity to be binding partners, which may mediate tau spread. Accumulation of tau in synapses correlated with synapse loss, and synaptic engulfment by astrocytes was observed, suggesting that astrocytes contribute to synapse loss. Together, these data indicate that targeting synaptic tau is a promising approach to treat PSP.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"13 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640385","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}
Annalisa Bucci, Marc Büttner, Niklas Domdei, Federica B. Rosselli, Matej Znidaric, Julian Bartram, Tobias Gänswein, Roland Diggelmann, Martina De Gennaro, Cameron S. Cowan, Wolf Harmening, Andreas Hierlemann, Botond Roska, Felix Franke
{"title":"Synchronization of visual perception within the human fovea","authors":"Annalisa Bucci, Marc Büttner, Niklas Domdei, Federica B. Rosselli, Matej Znidaric, Julian Bartram, Tobias Gänswein, Roland Diggelmann, Martina De Gennaro, Cameron S. Cowan, Wolf Harmening, Andreas Hierlemann, Botond Roska, Felix Franke","doi":"10.1038/s41593-025-02011-3","DOIUrl":"https://doi.org/10.1038/s41593-025-02011-3","url":null,"abstract":"<p>The human brain constructs a model of the world by processing sensory signals with distinct temporal characteristics that may differ in generation and transmission speed within a single sensory modality. To perceive simultaneous events as occurring at the same time, the brain must synchronize this sensory information, yet the mechanisms underlying such synchronization remain unclear. By combining human neural recordings, behavioral measurements and modeling, we show that in the human visual system, this process begins in the fovea centralis, the retinal region used for reading and recognizing faces. Reaction times to foveal single-cone photostimulation were similar across the central visual field, although visual information from neighboring foveal cones travels along axons of highly different lengths. From direct measurements of action potential propagation speeds, axon diameters and lengths in the human fovea centralis, we found that longer foveal axons have larger diameters and increased propagation speeds. We conclude that the human brain orchestrates axonal conduction speeds of unmyelinated axons in the retina to synchronize the arrival times of sensory signals. These results suggest a previously unknown mechanism by which the human brain synchronizes perception.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"4 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640386","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}
Rik Ossenkoppele, Emma M. Coomans, Liana G. Apostolova, Suzanne L. Baker, Henryk Barthel, Thomas G. Beach, Tammy L. S. Benzinger, Tobey Betthauser, Gérard N. Bischof, Michel Bottlaender, Pierick Bourgeat, Anouk den Braber, Matthias Brendel, Adam M. Brickman, David M. Cash, Maria C. Carrillo, William Coath, Bradley T. Christian, Brad C. Dickerson, Vincent Dore, Alexander Drzezga, Azadeh Feizpour, Wiesje M. van der Flier, Nicolai Franzmeier, Giovanni B. Frisoni, Valentina Garibotto, Elsmarieke van de Giessen, Juan Domingo-Gispert, Johannes Gnoerich, Yuna Gu, Yihui Guan, Bernard J. Hanseeuw, Theresa M. Harrison, Clifford R. Jack, Elena Jaeger, William J. Jagust, Willemijn J. Jansen, Renaud La Joie, Keith A. Johnson, Sterling C. Johnson, Ian A. Kennedy, Jun Pyo Kim, Koen van Laere, Julien Lagarde, Patrick Lao, José A. Luchsinger, Silke Kern, William C. Kreisl, Vincent Malotaux, Maura Malpetti, Jennifer J. Manly, Xiaoxie Mao, Niklas Mattsson-Carlgren, Konstantin Messerschmidt, Carolina Minguillon, Elizabeth M. Mormino, John T. O’Brien, Sebastian Palmqvist, Debora E. Peretti, Ron C. Petersen, Yolande A. L. Pijnenburg, Michael J. Pontecorvo, Judes Poirier, Gil D. Rabinovici, Nesrine Rahmouni, Shannon L. Risacher, Pedro Rosa-Neto, Howard Rosen, Christopher C. Rowe, James B. Rowe, Michael Rullmann, Yasmine Salman, Marie Sarazin, Andrew J. Saykin, Julie A. Schneider, Michael Schöll, Jonathan M. Schott, Sang Won Seo, Geidy E. Serrano, Sergey Shcherbinin, Mahnaz Shekari, Ingmar Skoog, Ruben Smith, Reisa A. Sperling, Laure Spruyt, Erik Stomrud, Olof Strandberg, Joseph Therriault, Fang Xie, Rik Vandenberghe, Victor L. Villemagne, Sylvia Villeneuve, Pieter Jelle Visser, Hillary Vossler, Christina B. Young, Colin Groot, Oskar Hansson
{"title":"Tau PET positivity in individuals with and without cognitive impairment varies with age, amyloid-β status, APOE genotype and sex","authors":"Rik Ossenkoppele, Emma M. Coomans, Liana G. Apostolova, Suzanne L. Baker, Henryk Barthel, Thomas G. Beach, Tammy L. S. Benzinger, Tobey Betthauser, Gérard N. Bischof, Michel Bottlaender, Pierick Bourgeat, Anouk den Braber, Matthias Brendel, Adam M. Brickman, David M. Cash, Maria C. Carrillo, William Coath, Bradley T. Christian, Brad C. Dickerson, Vincent Dore, Alexander Drzezga, Azadeh Feizpour, Wiesje M. van der Flier, Nicolai Franzmeier, Giovanni B. Frisoni, Valentina Garibotto, Elsmarieke van de Giessen, Juan Domingo-Gispert, Johannes Gnoerich, Yuna Gu, Yihui Guan, Bernard J. Hanseeuw, Theresa M. Harrison, Clifford R. Jack, Elena Jaeger, William J. Jagust, Willemijn J. Jansen, Renaud La Joie, Keith A. Johnson, Sterling C. Johnson, Ian A. Kennedy, Jun Pyo Kim, Koen van Laere, Julien Lagarde, Patrick Lao, José A. Luchsinger, Silke Kern, William C. Kreisl, Vincent Malotaux, Maura Malpetti, Jennifer J. Manly, Xiaoxie Mao, Niklas Mattsson-Carlgren, Konstantin Messerschmidt, Carolina Minguillon, Elizabeth M. Mormino, John T. O’Brien, Sebastian Palmqvist, Debora E. Peretti, Ron C. Petersen, Yolande A. L. Pijnenburg, Michael J. Pontecorvo, Judes Poirier, Gil D. Rabinovici, Nesrine Rahmouni, Shannon L. Risacher, Pedro Rosa-Neto, Howard Rosen, Christopher C. Rowe, James B. Rowe, Michael Rullmann, Yasmine Salman, Marie Sarazin, Andrew J. Saykin, Julie A. Schneider, Michael Schöll, Jonathan M. Schott, Sang Won Seo, Geidy E. Serrano, Sergey Shcherbinin, Mahnaz Shekari, Ingmar Skoog, Ruben Smith, Reisa A. Sperling, Laure Spruyt, Erik Stomrud, Olof Strandberg, Joseph Therriault, Fang Xie, Rik Vandenberghe, Victor L. Villemagne, Sylvia Villeneuve, Pieter Jelle Visser, Hillary Vossler, Christina B. Young, Colin Groot, Oskar Hansson","doi":"10.1038/s41593-025-02000-6","DOIUrl":"https://doi.org/10.1038/s41593-025-02000-6","url":null,"abstract":"<p>Tau positron emission tomography (PET) imaging allows in vivo detection of tau proteinopathy in Alzheimer’s disease, which is associated with neurodegeneration and cognitive decline. Understanding how demographic, clinical and genetic factors relate to tau PET positivity will facilitate its use for clinical practice and research. Here we conducted an analysis of 42 cohorts worldwide (<i>N</i> = 12,048), including 7,394 cognitively unimpaired (CU) participants, 2,177 participants with mild cognitive impairment (MCI) and 2,477 participants with dementia. We found that from age 60 years to 80 years, tau PET positivity in a temporal composite region increased from 1.1% to 4.4% among CU amyloid-β (Aβ)-negative participants and from 17.4% to 22.2% among CU Aβ-positive participants. Across the same age span, tau PET positivity decreased from 68.0% to 52.9% in participants with MCI and from 91.5% to 74.6% in participants with dementia. Age, Aβ status, <i>APOE</i> ε4 carriership and female sex were all associated with a higher prevalence of tau PET positivity across groups. <i>APOE</i> ε4 carriership in CU individuals lowered the age at onset of both Aβ positivity and tau positivity by decades. Finally, we replicated these associations in an independent autopsy dataset (<i>N</i> = 5,072 from 3 cohorts).</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"96 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640387","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}