Tanvi Butola, Melissa Hernández-Frausto, Stefan Blankvoort, Marcus Sandbukt Flatset, Lulu Peng, Ariel Hairston, Cara Deanne Johnson, Margot Elmaleh, Amanda Amilcar, Fabliha Hussain, Claudia Clopath, Clifford Kentros, Jayeeta Basu
{"title":"Hippocampus shapes entorhinal cortical output through a direct feedback circuit","authors":"Tanvi Butola, Melissa Hernández-Frausto, Stefan Blankvoort, Marcus Sandbukt Flatset, Lulu Peng, Ariel Hairston, Cara Deanne Johnson, Margot Elmaleh, Amanda Amilcar, Fabliha Hussain, Claudia Clopath, Clifford Kentros, Jayeeta Basu","doi":"10.1038/s41593-025-01883-9","DOIUrl":"https://doi.org/10.1038/s41593-025-01883-9","url":null,"abstract":"<p>Our brains integrate sensory, cognitive and internal state information with memories to extract behavioral relevance. Cortico–hippocampal interactions likely mediate this interplay, but underlying circuit mechanisms remain elusive. Unlike the entorhinal cortex-to-hippocampus pathway, we know little about the organization and function of the hippocampus-to-cortex feedback circuit. Here we report in mice, two functionally distinct parallel hippocampus-to-entorhinal cortex feedback pathways: the canonical disynaptic route via layer 5 and a novel monosynaptic input to layer 2/3. Circuit mapping reveals that hippocampal input predominantly drives excitation in layer 5 but feed-forward inhibition in layer 2/3. Upon repetitive pairing with cortical layer 1 inputs, hippocampal inputs undergo homosynaptic potentiation in layer 5, but induce heterosynaptic plasticity and spike output in layer 2/3. Behaviorally, hippocampal inputs to layer 5 and layer 2/3 support object memory encoding versus recall, respectively. Two-photon imaging during navigation reveals hippocampal suppression reduces spatially tuned cortical axonal activity. We present a model, where hippocampal feedback could iteratively shape ongoing cortical processing.</p>","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"47 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435148","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}
Louis-Philippe Bernier, Jasmin K. Hefendehl, R. Wilder Scott, Lin Wei Tung, Coral-Ann Lewis, Hesham Soliman, Stefan Simm, Lasse Dissing-Olesen, Jan Hofmann, David Guo, Murphy DeMeglio, Fabio M. Rossi, T. Michael Underhill, Brian A. MacVicar
{"title":"Brain pericytes and perivascular fibroblasts are stromal progenitors with dual functions in cerebrovascular regeneration after stroke","authors":"Louis-Philippe Bernier, Jasmin K. Hefendehl, R. Wilder Scott, Lin Wei Tung, Coral-Ann Lewis, Hesham Soliman, Stefan Simm, Lasse Dissing-Olesen, Jan Hofmann, David Guo, Murphy DeMeglio, Fabio M. Rossi, T. Michael Underhill, Brian A. MacVicar","doi":"10.1038/s41593-025-01872-y","DOIUrl":"10.1038/s41593-025-01872-y","url":null,"abstract":"Functional revascularization is key to stroke recovery and requires remodeling and regeneration of blood vessels around which is located the brain’s only stromal compartment. Stromal progenitor cells (SPCs) are critical for tissue regeneration following injury in many organs, yet their identity in the brain remains elusive. Here we show that the perivascular niche of brain SPCs includes pericytes, venular smooth muscle cells and perivascular fibroblasts that together help cerebral microvasculature regenerate following experimental stroke. Ischemic injury triggers amplification of pericytes and perivascular fibroblasts in the infarct region where they associate with endothelial cells inside a reactive astrocyte border. Fate-tracking of Hic1+ SPCs uncovered a transient functional and transcriptional phenotype of stroke-activated pericytes and perivascular fibroblasts. Both populations of these cells remained segregated, displaying distinct angiogenic and fibrogenic profiles. Therefore, pericytes and perivascular fibroblasts are distinct subpopulations of SPCs in the adult brain that coordinate revascularization and scar formation after injury. Bernier, Hefendehl et al. describe a stromal progenitor cell population consisting of pericytes, venular smooth muscle cells and perivascular fibroblasts in the adult brain that modify their function and coordinate blood vessel repair following stroke.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"517-535"},"PeriodicalIF":21.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427022","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}
Megha Sehgal, Daniel Almeida Filho, George Kastellakis, Sungsoo Kim, Jinsu Lee, Yang Shen, Shan Huang, Ayal Lavi, Giselle Fernandes, Irene Davila Mejia, Sunaina Soans Martin, Asli Pekcan, Melody Shana Wu, Won Do Heo, Panayiota Poirazi, Joshua T. Trachtenberg, Alcino J. Silva
{"title":"Compartmentalized dendritic plasticity in the mouse retrosplenial cortex links contextual memories formed close in time","authors":"Megha Sehgal, Daniel Almeida Filho, George Kastellakis, Sungsoo Kim, Jinsu Lee, Yang Shen, Shan Huang, Ayal Lavi, Giselle Fernandes, Irene Davila Mejia, Sunaina Soans Martin, Asli Pekcan, Melody Shana Wu, Won Do Heo, Panayiota Poirazi, Joshua T. Trachtenberg, Alcino J. Silva","doi":"10.1038/s41593-025-01876-8","DOIUrl":"10.1038/s41593-025-01876-8","url":null,"abstract":"Events occurring close in time are often linked in memory, and recent studies suggest that such memories are encoded by overlapping neuronal ensembles. However, the role of dendritic plasticity mechanisms in linking memories is unknown. Here we show that memory linking is dependent not only on neuronal ensemble overlap in the mouse retrosplenial cortex, but also on branch-specific dendritic allocation mechanisms. The same dendritic segments are preferentially activated by two linked (but not independent) contextual memories, and spine clusters added after each of two linked (but not independent) contextual memories are allocated to the same dendritic segments. Importantly, we show that the reactivation of dendrites activated during the first context exploration is sufficient to link two contextual memories. Our results demonstrate a critical role for localized dendritic plasticity in memory integration and reveal rules governing how linked and independent memories are allocated to dendritic compartments. Sehgal et al. show that branch-specific dendritic plasticity mechanisms in the retrosplenial cortex link memories acquired close in time such that, unlike independent memories, linked memories are encoded by many of the same dendritic branches.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"602-615"},"PeriodicalIF":21.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-025-01876-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427023","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}
Casey Paquola, Margaret Garber, Stefan Frässle, Jessica Royer, Yigu Zhou, Shahin Tavakol, Raul Rodriguez-Cruces, Donna Gift Cabalo, Sofie Valk, Simon B. Eickhoff, Daniel S. Margulies, Alan Evans, Katrin Amunts, Elizabeth Jefferies, Jonathan Smallwood, Boris C. Bernhardt
{"title":"Author Correction: The architecture of the human default mode network explored through cytoarchitecture, wiring and signal flow","authors":"Casey Paquola, Margaret Garber, Stefan Frässle, Jessica Royer, Yigu Zhou, Shahin Tavakol, Raul Rodriguez-Cruces, Donna Gift Cabalo, Sofie Valk, Simon B. Eickhoff, Daniel S. Margulies, Alan Evans, Katrin Amunts, Elizabeth Jefferies, Jonathan Smallwood, Boris C. Bernhardt","doi":"10.1038/s41593-025-01900-x","DOIUrl":"10.1038/s41593-025-01900-x","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"688-688"},"PeriodicalIF":21.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-025-01900-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143393355","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}
{"title":"Latent circuit inference from heterogeneous neural responses during cognitive tasks","authors":"Christopher Langdon, Tatiana A. Engel","doi":"10.1038/s41593-025-01869-7","DOIUrl":"10.1038/s41593-025-01869-7","url":null,"abstract":"Higher cortical areas carry a wide range of sensory, cognitive and motor signals mixed in heterogeneous responses of single neurons tuned to multiple task variables. Dimensionality reduction methods that rely on correlations between neural activity and task variables leave unknown how heterogeneous responses arise from connectivity to drive behavior. We develop the latent circuit model, a dimensionality reduction approach in which task variables interact via low-dimensional recurrent connectivity to produce behavioral output. We apply the latent circuit inference to recurrent neural networks trained to perform a context-dependent decision-making task and find a suppression mechanism in which contextual representations inhibit irrelevant sensory responses. We validate this mechanism by confirming the behavioral effects of patterned connectivity perturbations predicted by the latent circuit model. We find similar suppression of irrelevant sensory responses in the prefrontal cortex of monkeys performing the same task. We show that incorporating causal interactions among task variables is critical for identifying behaviorally relevant computations from neural response data. The latent circuit model identifies low-dimensional mechanisms of task execution from heterogenous neural responses. This approach reveals a latent inhibitory mechanism for context-dependent decisions in neural network models and the prefrontal cortex.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"665-675"},"PeriodicalIF":21.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-025-01869-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375429","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}
Tomas Vega-Zuniga, Anton Sumser, Olga Symonova, Peter Koppensteiner, Florian H. Schmidt, Maximilian Joesch
{"title":"A thalamic hub-and-spoke network enables visual perception during action by coordinating visuomotor dynamics","authors":"Tomas Vega-Zuniga, Anton Sumser, Olga Symonova, Peter Koppensteiner, Florian H. Schmidt, Maximilian Joesch","doi":"10.1038/s41593-025-01874-w","DOIUrl":"10.1038/s41593-025-01874-w","url":null,"abstract":"For accurate perception and motor control, an animal must distinguish between sensory experiences elicited by external stimuli and those elicited by its own actions. The diversity of behaviors and their complex influences on the senses make this distinction challenging. Here, we uncover an action–cue hub that coordinates motor commands with visual processing in the brain’s first visual relay. We show that the ventral lateral geniculate nucleus (vLGN) acts as a corollary discharge center, integrating visual translational optic flow signals with motor copies from saccades, locomotion and pupil dynamics. The vLGN relays these signals to correct action-specific visual distortions and to refine perception, as shown for the superior colliculus and in a depth-estimation task. Simultaneously, brain-wide vLGN projections drive corrective actions necessary for accurate visuomotor control. Our results reveal an extended corollary discharge architecture that refines early visual transformations and coordinates actions via a distributed hub-and-spoke network to enable visual perception during action. Animals must distinguish between signals from sensory stimuli and action-generated signals. This paper shows that the ventral lateral geniculate nucleus acts as a corollary discharge center to suppress motion-induced visual signals, orchestrating accurate perception and motor control.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 3","pages":"627-639"},"PeriodicalIF":21.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41593-025-01874-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375430","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}
{"title":"Prenatal stress effects on the placenta","authors":"Laura Zelenka","doi":"10.1038/s41593-025-01887-5","DOIUrl":"10.1038/s41593-025-01887-5","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"217-217"},"PeriodicalIF":21.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257831","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":"Charting the development of human dorsal root ganglia","authors":"George Andrew S. Inglis","doi":"10.1038/s41593-025-01885-7","DOIUrl":"10.1038/s41593-025-01885-7","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"217-217"},"PeriodicalIF":21.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257832","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":"Non-REM sleep substates separate old and new memories","authors":"Leonie Welberg","doi":"10.1038/s41593-025-01886-6","DOIUrl":"10.1038/s41593-025-01886-6","url":null,"abstract":"","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"217-217"},"PeriodicalIF":21.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143257830","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}
Sigrid Trägenap, David E. Whitney, David Fitzpatrick, Matthias Kaschube
{"title":"The developmental emergence of reliable cortical representations","authors":"Sigrid Trägenap, David E. Whitney, David Fitzpatrick, Matthias Kaschube","doi":"10.1038/s41593-024-01857-3","DOIUrl":"10.1038/s41593-024-01857-3","url":null,"abstract":"The fundamental structure of cortical networks arises early in development before the onset of sensory experience. However, how endogenously generated networks respond to the onset of sensory experience and how they form mature sensory representations with experience remain unclear. In this study, we examined this ‘nature–nurture transform’ at the single-trial level using chronic in vivo calcium imaging in ferret visual cortex. At eye opening, visual stimulation evokes robust patterns of modular cortical network activity that are highly variable within and across trials, severely limiting stimulus discriminability. These initial stimulus-evoked modular patterns are distinct from spontaneous network activity patterns present before and at the time of eye opening. Within a week of normal visual experience, cortical networks develop low-dimensional, highly reliable stimulus representations that correspond with reorganized patterns of spontaneous activity. Using a computational model, we propose that reliable visual representations derive from the alignment of feedforward and recurrent cortical networks shaped by novel patterns of visually driven activity. Sensory experience transforms endogenously structured cortical networks with diverse and unreliable visual responses into reliable representations. This process is proposed to involve the alignment of feedforward and recurrent networks.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"28 2","pages":"394-405"},"PeriodicalIF":21.2,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083422","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}