{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:09:23Z","timestamp":1790647763246,"version":"4.1.0"},"posted":{"date-parts":[[2026,6,9]]},"group-title":"Neuroscience","reference-count":52,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T00:00:00Z","timestamp":1780963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"crossref","award":["1RM1NS132981-01"],"award-info":[{"award-number":["1RM1NS132981-01"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Dendritic spines are the principal postsynaptic targets of excitatory synapses, yet the network logic governing their organization and contribution to cortical computation remains unclear. Here, we combine the MICrONS ultrastructural reconstruction of mouse visual cortex with matched\n                  <jats:italic>in vivo<\/jats:italic>\n                  two-photon calcium imaging to explore the network roles of dendritic spines. Structurally, we show that spine density predicts the number and diversity of both excitatory and inhibitory presynaptic partners, supporting the long-standing \u201cconnectivity and diversity\u201d hypothesis. Beyond expanding input space, spines exhibit distinct network-level principles: excitatory axons preferentially target spines with increasing axonal distance from the soma; highly broadcasting (\u201chub\u201d) neurons preferentially innervate spines; and neurons sharing presynaptic partners preferentially route their own outputs onto spines, revealing an input-to-spine\/output-to-spine wiring correlations. Functionally, we find that these same structural motifs are found in neuronal ensembles, defined as groups of neurons with correlated calcium activity. Ensemble members are interconnected at more than twice the rate of spatially matched controls; these synapses connecting them are routed almost exclusively onto dendritic spines; and their shared presynaptic partners are almost exclusively inhibitory neurons that themselves also preferentially target spines. We suggest that local recurrent spine-targeted excitation effectively binds ensemble members into a coactive subnetwork, while shared spine-directed inhibition gates, synchronizes, and stabilizes their collective activity, providing a circuit-level architecture that may support attractor dynamics, pattern completion, and other cortical computations.\n                <\/jats:p>","DOI":"10.64898\/2026.06.07.730704","type":"posted-content","created":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T09:35:15Z","timestamp":1780997715000},"source":"Crossref","is-referenced-by-count":1,"title":["Dendritic spines implement specific connectivity and support neuronal ensembles in cortical circuits"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2835-4674","authenticated-orcid":false,"given":"Dean","family":"Geckt","sequence":"first","affiliation":[{"name":"The Edmond and Lily Safra Center for Brain Science, The Hebrew University of Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7244-2348","authenticated-orcid":false,"given":"Netanel","family":"Ofer","sequence":"additional","affiliation":[{"name":"Department of Electrical and Electronics Engineering, Ariel University, Ariel, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3455-2367","authenticated-orcid":false,"given":"Michael W.","family":"Reimann","sequence":"additional","affiliation":[{"name":"Open Brain Institute, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4206-497X","authenticated-orcid":false,"given":"Rafael","family":"Yuste","sequence":"additional","affiliation":[{"name":"NeuroTechnology Center, Columbia University, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7279-9630","authenticated-orcid":false,"given":"Idan","family":"Segev","sequence":"additional","affiliation":[{"name":"The Edmond and Lily Safra Center for Brain Science, The Hebrew University of Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026081913152958000_2026.06.07.730704v2.1","doi-asserted-by":"crossref","first-page":"e77470","DOI":"10.7554\/eLife.77470","article-title":"Intrinsic excitability mechanisms of neuronal ensemble formation","volume":"11","year":"2022","journal-title":"eLife"},{"key":"2026081913152958000_2026.06.07.730704v2.2","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-025-02004-2"},{"key":"2026081913152958000_2026.06.07.730704v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4286"},{"key":"2026081913152958000_2026.06.07.730704v2.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.023"},{"key":"2026081913152958000_2026.06.07.730704v2.5","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5214-14.2015"},{"key":"2026081913152958000_2026.06.07.730704v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2012.02.030"},{"key":"2026081913152958000_2026.06.07.730704v2.7","doi-asserted-by":"publisher","DOI":"10.1126\/science.abg0501"},{"key":"2026081913152958000_2026.06.07.730704v2.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature14182"},{"key":"2026081913152958000_2026.06.07.730704v2.9","unstructured":"Dorkenwald, S. , Schneider-Mizell, C. and Collman, F . (2020). MeshParty: v1.9.0. Zenodo. Software."},{"key":"2026081913152958000_2026.06.07.730704v2.10","doi-asserted-by":"crossref","first-page":"1550","DOI":"10.1016\/j.celrep.2017.10.035","article-title":"Timed synaptic inhibition shapes NMDA spikes, influencing local dendritic processing and global I\/O properties of cortical neurons","volume":"21","year":"2017","journal-title":"Cell Reports"},{"key":"2026081913152958000_2026.06.07.730704v2.11","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.27.070203.144152"},{"key":"2026081913152958000_2026.06.07.730704v2.12","doi-asserted-by":"crossref","first-page":"e1011891","DOI":"10.1371\/journal.pcbi.1011891","article-title":"Cortical cell assemblies and their underlying connectivity: An in silico study","volume":"20","year":"2024","journal-title":"PLOS Computational Biology"},{"key":"2026081913152958000_2026.06.07.730704v2.13","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07765-7"},{"key":"2026081913152958000_2026.06.07.730704v2.14","doi-asserted-by":"crossref","unstructured":"Fanutza, T. , Popp, Y. , Brueckner, A. M. , Hertrich, N. , Sivers, J. V. , Larkum, M. et al. (2025). Shaft versus spine localization affects the structural plasticity of glutamatergic synapses. bioRxiv 2025.","DOI":"10.64898\/2025.12.05.692591"},{"key":"2026081913152958000_2026.06.07.730704v2.15","doi-asserted-by":"publisher","DOI":"10.1038\/nature10844"},{"key":"2026081913152958000_2026.06.07.730704v2.16","doi-asserted-by":"publisher","DOI":"10.1038\/nn.4576"},{"key":"2026081913152958000_2026.06.07.730704v2.17","first-page":"70","article-title":"The dip test of unimodality","volume":"13","year":"1985","journal-title":"The Annals of Statistics"},{"key":"2026081913152958000_2026.06.07.730704v2.18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0251647"},{"key":"2026081913152958000_2026.06.07.730704v2.19","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.044784"},{"key":"2026081913152958000_2026.06.07.730704v2.20","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.8.2554"},{"key":"2026081913152958000_2026.06.07.730704v2.21","doi-asserted-by":"publisher","DOI":"10.1038\/nature09880"},{"key":"2026081913152958000_2026.06.07.730704v2.22","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.13-02-00413.1993"},{"key":"2026081913152958000_2026.06.07.730704v2.23","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhy143"},{"key":"2026081913152958000_2026.06.07.730704v2.24","doi-asserted-by":"crossref","unstructured":"Loomba, S. , Straehle, J. , Gangadharan, V. , Heike, N. , Khalifa, A. , Motta, A. et al. (2022). Connectomic comparison of mouse and human cortex. Science 377, eabo0924.","DOI":"10.1126\/science.abo0924"},{"key":"2026081913152958000_2026.06.07.730704v2.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2013.04.010"},{"key":"2026081913152958000_2026.06.07.730704v2.26","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(00)00496-6"},{"key":"2026081913152958000_2026.06.07.730704v2.27","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-025-08790-w"},{"key":"2026081913152958000_2026.06.07.730704v2.28","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0511-07.2007"},{"key":"2026081913152958000_2026.06.07.730704v2.29","doi-asserted-by":"crossref","unstructured":"Ofer, N. , Shapira, S. and Segev, I . (2026). Spine-neck electrical bottlenecks tune temporal precision and inhibitory gating in cortical pyramidal neurons: A connectomics-based biophysical study. bioRxiv 2026.","DOI":"10.64898\/2026.02.16.706119"},{"key":"2026081913152958000_2026.06.07.730704v2.30","doi-asserted-by":"crossref","unstructured":"Pedigo, B. D. , Danskin, B. P. , Swanstrom, R. , Neace, E. , Dorkenwald, S. , da Costa, N. M. et al. (2026). A quantitative census of millions of postsynaptic structures in a large electron microscopy volume of mouse visual cortex. bioRxiv 2026.","DOI":"10.64898\/2026.02.19.706834"},{"key":"2026081913152958000_2026.06.07.730704v2.31","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016051108"},{"key":"2026081913152958000_2026.06.07.730704v2.32","unstructured":"Peters, A. , Palay, S. L. and Webster, H. D . (1991). The Fine Structure of the Nervous System. Oxford University Press, New York."},{"key":"2026081913152958000_2026.06.07.730704v2.33","doi-asserted-by":"publisher","DOI":"10.1038\/nature07709"},{"key":"2026081913152958000_2026.06.07.730704v2.34","doi-asserted-by":"crossref","unstructured":"Piazza, B. , Barab\u00e1si, D. L. , Ferreira Castro, A. , Menichetti, G. and Barab\u00e1si, A.-L . (2025). Physical network constraints define the lognormal architecture of the brain\u2019s connectome. bioRxiv 2025.","DOI":"10.1101\/2025.02.27.640551"},{"key":"2026081913152958000_2026.06.07.730704v2.35","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(74)85948-5"},{"key":"2026081913152958000_2026.06.07.730704v2.36","doi-asserted-by":"crossref","unstructured":"Santander, D. E. , Pokorny, C. , Ecker, A. , Lazovskis, J. , Santoro, M. , Smith, J. P. , Hess, K. , Levi, R. and Reimann, M. W . (2025). Heterogeneous and higher-order cortical connectivity undergirds efficient, robust, and reliable neural codes. IScience 28.","DOI":"10.1016\/j.isci.2024.111585"},{"key":"2026081913152958000_2026.06.07.730704v2.37","doi-asserted-by":"publisher","DOI":"10.1038\/nature24005"},{"key":"2026081913152958000_2026.06.07.730704v2.38","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07780-8"},{"key":"2026081913152958000_2026.06.07.730704v2.39","doi-asserted-by":"publisher","DOI":"10.1152\/jn.1988.60.2.499"},{"key":"2026081913152958000_2026.06.07.730704v2.40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030068"},{"key":"2026081913152958000_2026.06.07.730704v2.41","doi-asserted-by":"publisher","DOI":"10.1126\/science.1210362"},{"key":"2026081913152958000_2026.06.07.730704v2.42","doi-asserted-by":"crossref","first-page":"4276","DOI":"10.1038\/s41467-020-17861-7","article-title":"A spike-timing-dependent plasticity rule for dendritic spines","volume":"11","year":"2020","journal-title":"Nature communications"},{"key":"2026081913152958000_2026.06.07.730704v2.43","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3539-11.2011"},{"key":"2026081913152958000_2026.06.07.730704v2.44","doi-asserted-by":"crossref","unstructured":"Wagner-Carena, S. , Kate, S. , Riordan, T. , Abbasi-Asl, R. , Aman, J. , Amster, A. , Berteau, S. et al. (2025). Hebb\u2019s Vision: The Structural Underpinnings of Hebbian Assemblies. bioRxiv 2025.","DOI":"10.1101\/2025.04.24.649900"},{"key":"2026081913152958000_2026.06.07.730704v2.45","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.07.024"},{"key":"2026081913152958000_2026.06.07.730704v2.46","unstructured":"Yuste, R. (2023). Dendritic Spines. MIT Press."},{"key":"2026081913152958000_2026.06.07.730704v2.47","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1152\/physrev.00003.2025","article-title":"Neuronal ensembles in cortical function and disease","volume":"106","year":"2026","journal-title":"Physiological Reviews"},{"key":"2026081913152958000_2026.06.07.730704v2.48","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.24.1.1071"},{"key":"2026081913152958000_2026.06.07.730704v2.49","doi-asserted-by":"publisher","DOI":"10.1038\/nrn1300"},{"key":"2026081913152958000_2026.06.07.730704v2.50","doi-asserted-by":"publisher","DOI":"10.1038\/375682a0"},{"key":"2026081913152958000_2026.06.07.730704v2.51","doi-asserted-by":"crossref","unstructured":"Zhang, C. , Schneider-Mizell, C. M. , Danskin, B. P. , Swanstrom, R. , Neace, E. , Joyce, E. et al. (2026). Cell-type-specific parallel pathways in the canonical cortical microcircuit. bioRxiv 2026.","DOI":"10.64898\/2026.04.23.720412"},{"key":"2026081913152958000_2026.06.07.730704v2.52","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.10.054"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.06.07.730704","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T20:15:38Z","timestamp":1787170538000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.06.07.730704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,9]]},"references-count":52,"URL":"https:\/\/doi.org\/10.64898\/2026.06.07.730704","relation":{},"subject":[],"published":{"date-parts":[[2026,6,9]]},"subtype":"preprint"}}