NeuronPub Date : 2025-09-12DOI: 10.1016/j.neuron.2025.08.018
Katherine R Croce, Christopher Ng, Serihy Pankiv, Eddy Albarran, Peter Langfelder, Ana Ramos de Jesus, Glenn M Duncan, Nan Wang, Anna Basile, Caitlin McHugh, Nicole A Litt, Alina Li, Sophia Friedman, Etty P Cortes, Michael C Zody, X William Yang, Jun B Ding, Jean Paul G Vonsattel, Anne Simonsen, David E Housman, Nancy S Wexler, Ai Yamamoto
{"title":"A rare genetic variant confers resistance to neurodegeneration across multiple neurological disorders by augmenting selective autophagy.","authors":"Katherine R Croce, Christopher Ng, Serihy Pankiv, Eddy Albarran, Peter Langfelder, Ana Ramos de Jesus, Glenn M Duncan, Nan Wang, Anna Basile, Caitlin McHugh, Nicole A Litt, Alina Li, Sophia Friedman, Etty P Cortes, Michael C Zody, X William Yang, Jun B Ding, Jean Paul G Vonsattel, Anne Simonsen, David E Housman, Nancy S Wexler, Ai Yamamoto","doi":"10.1016/j.neuron.2025.08.018","DOIUrl":"10.1016/j.neuron.2025.08.018","url":null,"abstract":"<p><p>The study of disease modifiers is a powerful way to identify patho-mechanisms associated with disease. Using the strong genetic traits of Huntington's disease (HD), we identified a rare, single-nucleotide polymorphism (SNP) in WDFY3 associated with a delayed age of onset of up to 23 years. Remarkably, the introduction of the orthologous SNP into mice recapitulates this neuroprotection, significantly delaying neuropathological and behavioral dysfunction in two models of HD. The SNP increases expression of the protein autophagy-linked Fab1, YOTB, Vac1, and EEA1 (FYVE) protein (Alfy), an autophagy adaptor protein for the clearance of aggregated proteins, whose ectopic overexpression is sufficient to capture the neuroprotective effects of the variant. Increasing Alfy expression protects not only against HD but also against the toxicity due to phospho-α-synuclein and AT8-positive accumulation. By combining human and mouse genetics, we have uncovered a pathway that protects against multiple proteinopathies, revealing a much-sought-after, shared therapeutic target across a broad range of neurodegenerative diseases.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuronPub Date : 2025-09-11DOI: 10.1016/j.neuron.2025.08.016
Taylor Landry, Laura Perrault, David Melville, Zhe Chen, Ya-Dong Li, Ping Dong, W Todd Farmer, Brent Asrican, Hannah Lee, Libo Zhang, Ryan N Sheehy, Corina Damian, Thomas Collins, Nehemiah Stewart, E S Anton, Juan Song
{"title":"Targeting glucose-inhibited hippocampal CCK interneurons prevents cognitive impairment in diet-induced obesity.","authors":"Taylor Landry, Laura Perrault, David Melville, Zhe Chen, Ya-Dong Li, Ping Dong, W Todd Farmer, Brent Asrican, Hannah Lee, Libo Zhang, Ryan N Sheehy, Corina Damian, Thomas Collins, Nehemiah Stewart, E S Anton, Juan Song","doi":"10.1016/j.neuron.2025.08.016","DOIUrl":"10.1016/j.neuron.2025.08.016","url":null,"abstract":"<p><p>Metabolic disorders are closely linked to increased risk of cognitive decline, with Western-style high-fat diets (HFDs) emerging as key contributors. However, the underlying cellular and molecular mechanisms remain unclear. Here, we demonstrate that short-term HFD (stHFD) consumption disrupts memory processing by inducing hyperactivity in dentate gyrus (DG) cholecystokinin-expressing interneurons (CCK-INs). We identify DG CCK-INs as glucose-inhibited neurons that become hyperactive in response to stHFD-induced reductions in DG glucose availability, coinciding with increased phosphorylation of the glycolytic enzyme pyruvate kinase M2 (PKM2). Restoring glucose availability, reducing PKM2 expression, or inhibiting PKM2 activity normalizes CCK-IN activity and rescues memory deficits. Furthermore, interventions preventing CCK-IN hyperactivity or PKM2 phosphorylation protect against long-term cognitive impairments in a diet-induced obesity mouse model. These findings reveal a previously unrecognized mechanism by which dietary metabolic stress disrupts hippocampal function and highlight DG CCK-INs and PKM2 as promising therapeutic targets for preventing cognitive decline associated with metabolic disorders.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuronPub Date : 2025-09-11DOI: 10.1016/j.neuron.2025.08.013
Bart Lodder, Tarun Kamath, Ecaterina Savenco, Berend Röring, Michelle Siegel, Julie A Chouinard, Suk Joon Lee, Caroline Zagoren, Paul Rosen, Isa Hartman, Joshua Timmins, Roger Adan, Lin Tian, Bernardo L Sabatini
{"title":"Absolute measurement of fast and slow neuronal signals with fluorescence lifetime photometry at high temporal resolution.","authors":"Bart Lodder, Tarun Kamath, Ecaterina Savenco, Berend Röring, Michelle Siegel, Julie A Chouinard, Suk Joon Lee, Caroline Zagoren, Paul Rosen, Isa Hartman, Joshua Timmins, Roger Adan, Lin Tian, Bernardo L Sabatini","doi":"10.1016/j.neuron.2025.08.013","DOIUrl":"10.1016/j.neuron.2025.08.013","url":null,"abstract":"<p><p>Dynamic signaling by extracellular and intracellular molecules impacts downstream pathways in a cell-type-specific manner. Fluorescent reporters of such signals are typically optimized to detect fast, relative changes in concentration of target molecules. They are less well suited to detect slowly changing signals and rarely provide absolute measurements. Here, we developed fluorescence lifetime photometry at high temporal resolution (FLIPR), which utilizes frequency-domain analog processing to measure the absolute fluorescence lifetime of genetically encoded sensors at high speed but with long-term stability and picosecond precision. We applied FLIPR to investigate dopamine signaling in functionally distinct striatal subregions. We observed higher tonic dopamine levels in the tail of the striatum compared with the nucleus accumbens core and differential and dynamic responses in phasic and tonic dopamine to appetitive and aversive stimuli. Thus, FLIPR reports fast and slow timescale neuronal signaling in absolute units, revealing previously unappreciated spatial and temporal variation even in well-studied signaling systems.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145054728","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}
NeuronPub Date : 2025-09-10DOI: 10.1016/j.neuron.2025.08.031
Weiping Han, Jeong-Seop Rhee, Anton Maximov, Ye Lao, Tomoyuki Mashimo, Christian Rosenmund, Thomas C Südhof
{"title":"N-Glycosylation Is Essential for Vesicular Targeting of Synaptotagmin 1.","authors":"Weiping Han, Jeong-Seop Rhee, Anton Maximov, Ye Lao, Tomoyuki Mashimo, Christian Rosenmund, Thomas C Südhof","doi":"10.1016/j.neuron.2025.08.031","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.08.031","url":null,"abstract":"","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040927","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}
NeuronPub Date : 2025-09-10DOI: 10.1016/j.neuron.2025.08.014
Augusto Abel Lempel, Sigrid Trägenap, Clara Tepohl, Matthias Kaschube, David Fitzpatrick
{"title":"Development of coherent cortical responses reflects increased discriminability of feedforward inputs and their alignment with recurrent circuits.","authors":"Augusto Abel Lempel, Sigrid Trägenap, Clara Tepohl, Matthias Kaschube, David Fitzpatrick","doi":"10.1016/j.neuron.2025.08.014","DOIUrl":"10.1016/j.neuron.2025.08.014","url":null,"abstract":"<p><p>Sensory cortical areas guide behavior by transforming stimulus-driven inputs into reliable activity patterns. In the visual cortex, layer 4 (L4) neurons activated by the same edge orientation provide feedforward input to layers 2/3 (L2/3) modules sharing strong recurrent connections. This alignment facilitates selective amplification, driving a reliable, modular representation of orientation, but how it develops remains unclear. Using electrophysiology and calcium imaging, we find that in visually naive animals, L4-L2/3 coactivity lacks orientation specificity. One contributing factor is low orientation discriminability in L4, which improves with experience. However, computational modeling indicates that misaligned feedforward-recurrent interactions also play a critical role and predict developmental changes in tuning dynamics of sustained L2/3 responses, which we confirm with whole-cell recordings. Altogether, our study provides evidence that enhanced discriminability of L4 feedforward inputs and their alignment with recurrent L2/3 interactions following experience contribute to the development of reliable sensory representations with laminar-temporal coherence.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12462903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040971","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
NeuronPub Date : 2025-09-09DOI: 10.1016/j.neuron.2025.08.012
Yu Huo, Xingyuan Wang, Xiaorui Lin, Jiaojiao Yu, Binlong Li, Zepeng Liu, Shengyang Guo, Yutong Wang, Rongchun Tang, Bofei Li, Shunjie Zhang, Yunke Zhang, Zhehan Jiang, Xiang Fan, Xinzhi Ye, Yifan Li, Xinyu Zhang, Yun Yao, Sen Song, Mao Xu, Hong Jiang, Guogang Xing, You Wan, Cailian Cui, Yijing Li, Linlin Sun
{"title":"Corticotropin-releasing hormone signaling from piriform cortex to amygdala mediates social homophily in opioid addiction.","authors":"Yu Huo, Xingyuan Wang, Xiaorui Lin, Jiaojiao Yu, Binlong Li, Zepeng Liu, Shengyang Guo, Yutong Wang, Rongchun Tang, Bofei Li, Shunjie Zhang, Yunke Zhang, Zhehan Jiang, Xiang Fan, Xinzhi Ye, Yifan Li, Xinyu Zhang, Yun Yao, Sen Song, Mao Xu, Hong Jiang, Guogang Xing, You Wan, Cailian Cui, Yijing Li, Linlin Sun","doi":"10.1016/j.neuron.2025.08.012","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.08.012","url":null,"abstract":"<p><p>Social partner selection can significantly influence one's social well-being, emotional support, and even cognitive functions. Drug-abstinent mice exhibit sociability deficits, yet how drug-addicted individuals select their social partners and how these choices influence addiction-related behaviors remain unclear. In this study, we demonstrate that opioid-experienced mice prefer socializing with opioid-experienced peers. Presentation of an opioid-abstinent demonstrator mouse or its olfactory cues (not ultrasound or visual cues) enhances corticotropin-releasing hormone (CRH) release from the anterior piriform cortex (APIR) to the basomedial amygdala (BMA) in abstinent observer mice. This CRH release occurs specifically during approach, acts through CRH receptor 1/2 in the BMA, and enhances social motivation. Disruption of this social homophily impairs addiction-related memory and relapse in opioid-abstinent mice. Our findings reveal social homophily in opioid-experienced individuals, elucidate the underlying APIR-BMA CRH signaling mechanism, and underscore the importance of social support from non-addicted peers for opioid-abstinent individuals during recovery.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":""},"PeriodicalIF":15.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058575","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}
NeuronPub Date : 2025-09-03DOI: 10.1016/j.neuron.2025.08.003
Matthia A Karreman, Frank Winkler
{"title":"Cancer neuroscience of brain metastasis: When in Rome, do as the Romans do.","authors":"Matthia A Karreman, Frank Winkler","doi":"10.1016/j.neuron.2025.08.003","DOIUrl":"https://doi.org/10.1016/j.neuron.2025.08.003","url":null,"abstract":"<p><p>It is becoming increasingly clear that the nervous system and cancer execute an intimate crosstalk, influencing cancer initiation, growth, spread, and resistance mechanisms. Cancer, vice versa, can change the nervous system. These mostly harmful neuro-cancer interactions constitute the emerging field of \"cancer neuroscience.\" Although this crosstalk is not limited to the central nervous system, the brain remains the site of particularly strong neural influences. In this review, we use the extensive knowledge of neuro-cancer interactions in primary brain tumors to highlight new discoveries about how neural influences govern metastatic tumor cells that originate from outside the brain and how, in turn, these cells can plastically modify the brain and its functions. Thus, we use brain metastasis, a particularly devastating complication of several common cancers, as a roadmap to conceptualize how far-reaching neuro-cancer interactions throughout the body can be and develop new ideas on how to use these insights for improved therapies.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 17","pages":"2740-2759"},"PeriodicalIF":15.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001014","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}
NeuronPub Date : 2025-09-03Epub Date: 2025-08-13DOI: 10.1016/j.neuron.2025.07.016
Jessica S Chadwick, Charlotte Decourt, Franziska Müller, Ines Maldonado-Lasuncion, Elisabeth Serger, Guiping Kong, Luming Zhou, Yayue Song, Yuyang Yan, Zhulin Yuan, Alessandro Falconieri, Phoebe Liddell, Linshan Chu, Wei Qin Chan, Lucia Luengo-Gutierrez, Ilaria Palmisano, Simone Di Giovanni
{"title":"Dietary-dependent sensitization of neuronal leptin signaling promotes neural repair after injury via cAMP and gene transcription.","authors":"Jessica S Chadwick, Charlotte Decourt, Franziska Müller, Ines Maldonado-Lasuncion, Elisabeth Serger, Guiping Kong, Luming Zhou, Yayue Song, Yuyang Yan, Zhulin Yuan, Alessandro Falconieri, Phoebe Liddell, Linshan Chu, Wei Qin Chan, Lucia Luengo-Gutierrez, Ilaria Palmisano, Simone Di Giovanni","doi":"10.1016/j.neuron.2025.07.016","DOIUrl":"10.1016/j.neuron.2025.07.016","url":null,"abstract":"<p><p>Dietary-dependent shifts, ranging from metabolic dysfunction to health, involve transitions in key signaling pathways. Dietary regimens can influence nervous system repair, but whether conserved, diet-specific mechanisms can enhance neuronal regeneration by directly sensitizing neuronal signaling remains unclear. We found that in mice, in contrast to a neuropathy-inducing high-fat diet that causes leptin resistance, intermittent fasting (IF) enhances leptin sensitivity in dorsal root ganglia sensory neurons. Deletion of leptin receptors in sensory neurons impairs IF-induced regeneration. Systemic leptin or leptin neuronal overexpression promote axonal repair after sciatic nerve crush and spinal cord injury via endocrine or autocrine mechanism, respectively. Leptin-dependent axon growth requires cyclic AMP (cAMP) signaling, transcriptional activity, and regenerative gene expression to support axon growth after injury. Unexpectedly, leptin, whose canonical function is to control feeding, promotes neuronal regenerative signaling, highlighting a novel role in nervous system regeneration and providing insights into diet-dependent neurorepair mechanisms.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2839-2855.e8"},"PeriodicalIF":15.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855840","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}
NeuronPub Date : 2025-09-03DOI: 10.1016/j.neuron.2025.07.017
Debpali Sur, Yi Zeng, Hiroki Kobayashi, Xiaofei Zhi, Mara R Goetz, Clara M Müller, Anastasia-Maria Zavitsanou, Caroline C Picoli, Andre A Martel Matos, Javier Pareja, Brajesh K Savita, Taeho Lee, Jair P Cunha-Junior, Jaime Henrique Amorim, Amin Reza Nikpoor, Alissa Dory, Ajitha Thanabalasuriar, Pedro A F Galante, Vincent T Ma, Aaron W James, Andrew J Shepherd, Madeleine J Oudin, Yuri L Bunimovich, Nicole N Scheff, Nisha J D'Silva, Karen O Dixon, Ishmail Abdus-Saboor, Timothy C Wang, Sebastien Talbot, Alexander Birbrair
{"title":"Entangled cellular and molecular relationships at the sensory neuron-cancer interface.","authors":"Debpali Sur, Yi Zeng, Hiroki Kobayashi, Xiaofei Zhi, Mara R Goetz, Clara M Müller, Anastasia-Maria Zavitsanou, Caroline C Picoli, Andre A Martel Matos, Javier Pareja, Brajesh K Savita, Taeho Lee, Jair P Cunha-Junior, Jaime Henrique Amorim, Amin Reza Nikpoor, Alissa Dory, Ajitha Thanabalasuriar, Pedro A F Galante, Vincent T Ma, Aaron W James, Andrew J Shepherd, Madeleine J Oudin, Yuri L Bunimovich, Nicole N Scheff, Nisha J D'Silva, Karen O Dixon, Ishmail Abdus-Saboor, Timothy C Wang, Sebastien Talbot, Alexander Birbrair","doi":"10.1016/j.neuron.2025.07.017","DOIUrl":"10.1016/j.neuron.2025.07.017","url":null,"abstract":"<p><p>Peripheral sensory neurons, once regarded merely as a passive route for nociceptive signals, are now acknowledged as active participants in solid tumor progression. This review explores how sensory neurons influence and are influenced by the tumor microenvironment (TME) through both chemical and electrical signaling, underscoring their pivotal role in the emerging field of cancer neuroscience. We summarize recent findings indicating that cancer-neuron interactions vary among different organs and experimental models, highlighting the ways in which various tumors recruit and reprogram sensory neurons to establish mutual communication loops that foster malignancy. Clinically, the degree of sensory innervation and the level of neuropeptide signaling show promise as diagnostic and prognostic biomarkers, while targeting these pathways may enhance the efficacy of standard cancer treatments. This review also highlights current knowledge gaps and proposes future research directions aimed at disrupting sensory neuron-tumor interactions, with the ultimate goal of improving clinical outcomes across multiple cancer types.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":"113 17","pages":"2760-2790"},"PeriodicalIF":15.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001011","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}
NeuronPub Date : 2025-09-03Epub Date: 2025-08-15DOI: 10.1016/j.neuron.2025.07.020
Hung Lo, Walter Cañedo Riedel, Malinda L S Tantirigama, Anke Schoenherr, Laura Moreno Velasquez, Lukas Faiss, Amit Kumar, Aileen Hakus, Benjamin R Rost, Matthew E Larkum, Benjamin Judkewitz, Katharina Stumpenhorst, Marion Rivalan, York Winter, Eleonora Russo, Wolfgang Kelsch, Dietmar Schmitz, Friedrich W Johenning
{"title":"Feeding-induced olfactory cortex suppression reduces satiation.","authors":"Hung Lo, Walter Cañedo Riedel, Malinda L S Tantirigama, Anke Schoenherr, Laura Moreno Velasquez, Lukas Faiss, Amit Kumar, Aileen Hakus, Benjamin R Rost, Matthew E Larkum, Benjamin Judkewitz, Katharina Stumpenhorst, Marion Rivalan, York Winter, Eleonora Russo, Wolfgang Kelsch, Dietmar Schmitz, Friedrich W Johenning","doi":"10.1016/j.neuron.2025.07.020","DOIUrl":"10.1016/j.neuron.2025.07.020","url":null,"abstract":"<p><p>Binge feeding commonly leads to overeating. Experiencing flavor during food consumption contributes to satiation. Still, the interactions between flavor, binge feeding, and food intake remain unknown. Using miniscopes for in vivo calcium imaging in the anterior piriform cortex (aPC) in freely moving mice, we identified specific excitatory neuronal responses to different food flavors during slow feeding. Switching from slow feeding to binge feeding transformed these specific responses into an unspecific global suppression of neuronal activity. Consummatory aPC suppression scaled with food value. GABAergic neurons in the olfactory tubercle (OT) projected to the aPC and mirrored activity patterns in the aPC under different feeding conditions, consistent with transmitting a value signal. Closed-loop optogenetic manipulations demonstrated that suppressing the aPC during binge bouts reduces satiation by selectively prolonging feeding bouts. We propose that aPC suppression by the OT enhances food intake by reducing sensory satiation during binge feeding-associated states of high motivation.</p>","PeriodicalId":19313,"journal":{"name":"Neuron","volume":" ","pages":"2856-2871.e8"},"PeriodicalIF":15.0,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862360","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}
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