{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T23:11:18Z","timestamp":1771369878403,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1012727","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000}}],"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T00:00:00Z","timestamp":1762387200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010664","name":"H2020 Future and Emerging Technologies","doi-asserted-by":"publisher","award":["964877"],"award-info":[{"award-number":["964877"]}],"id":[{"id":"10.13039\/100010664","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010664","name":"H2020 Future and Emerging Technologies","doi-asserted-by":"publisher","award":["964877"],"award-info":[{"award-number":["964877"]}],"id":[{"id":"10.13039\/100010664","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2022-137713NB-C22"],"award-info":[{"award-number":["PID2022-137713NB-C22"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003030","name":"Ag\u00e8ncia de Gesti\u00f3 d\u2019Ajuts Universitaris i de Recerca","doi-asserted-by":"publisher","award":["2021-SGR-00450"],"award-info":[{"award-number":["2021-SGR-00450"]}],"id":[{"id":"10.13039\/501100003030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011033","name":"Agencia Estatal de Investigaci\u00f3n","doi-asserted-by":"publisher","award":["PID2021-127311NB-I00"],"award-info":[{"award-number":["PID2021-127311NB-I00"]}],"id":[{"id":"10.13039\/501100011033","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Research Council","award":["101167121"],"award-info":[{"award-number":["101167121"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>An inherent challenge in designing laboratory-grown, engineered living neuronal networks lies in predicting the dynamic repertoire of the resulting network and its sensitivity to experimental variables. To fill this gap, and inspired by recent experimental studies, we present a numerical model designed to replicate the anisotropies in connectivity introduced through engineering, characterize the emergent collective behavior of the neuronal network, and make predictions. The numerical model is developed to replicate experimental data, and subsequently used to quantify network dynamics in relation to tunable structural and dynamical parameters. These include the strength of imprinted anisotropies, synaptic noise, and average axon lengths. We show that the model successfully captures the behavior of engineered neuronal cultures, revealing a rich repertoire of activity patterns that are highly sensitive to connectivity architecture and noise levels. Specifically, the imprinted anisotropies promote modularity and high clustering coefficients, substantially reducing the pathological-like bursting of standard neuronal cultures, whereas noise and axonal length influence the variability in dynamical states and activity propagation velocities. Moreover, connectivity anisotropies significantly enhance the ability to reconstruct structural connectivity from activity data, an aspect that is important to understand the structure-function relationship in neuronal networks. Our work provides a robust in silico framework to assist experimentalists in the design of in vitro neuronal systems and in anticipating their outcomes. This predictive capability is particularly valuable in developing reliable brain-on-a-chip platforms and in exploring fundamental aspects of neural computation, including input-output relationships and information coding.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1012727","type":"journal-article","created":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T18:42:59Z","timestamp":1762454579000},"page":"e1012727","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Role of connectivity anisotropies in the dynamics of cultured neuronal networks"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8215-7882","authenticated-orcid":true,"given":"Akke Mats","family":"Houben","sequence":"first","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3716-7520","authenticated-orcid":true,"given":"Jordi","family":"Garcia-Ojalvo","sequence":"additional","affiliation":[]},{"given":"Jordi","family":"Soriano","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2025,11,6]]},"reference":[{"issue":"4","key":"pcbi.1012727.ref001","first-page":"501","article-title":"Over a century of neuron culture: from the hanging drop to microfluidic devices","volume":"85","author":"LJ Millet","year":"2012","journal-title":"Yale J Biol Med"},{"key":"pcbi.1012727.ref002","doi-asserted-by":"crossref","unstructured":"Keller JM, Frega M. Past, present, and future of neuronal models in vitro. In: In vitro neuronal networks: from culturing methods to neuro-technological applications. 2019. p. 3\u201317.","DOI":"10.1007\/978-3-030-11135-9_1"},{"key":"pcbi.1012727.ref003","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.trac.2016.01.025","article-title":"\u201cBrains on a chip\u201d: Towards engineered neural networks","volume":"78","author":"MJ Aebersold","year":"2016","journal-title":"TrAC Trends in Analytical Chemistry"},{"issue":"1","key":"pcbi.1012727.ref004","doi-asserted-by":"crossref","first-page":"181","DOI":"10.3390\/biophysica3010012","article-title":"Neuronal cultures: exploring biophysics, complex systems, and medicine in a dish","volume":"3","author":"J Soriano","year":"2023","journal-title":"Biophysica"},{"issue":"5","key":"pcbi.1012727.ref005","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0002088","article-title":"Long-term activity-dependent plasticity of action potential propagation delay and amplitude in cortical networks","volume":"3","author":"DJ Bakkum","year":"2008","journal-title":"PLoS One"},{"issue":"2","key":"pcbi.1012727.ref006","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/S0006-3495(99)77234-6","article-title":"Simultaneous induction of pathway-specific potentiation and depression in networks of cortical neurons","volume":"76","author":"Y Jimbo","year":"1999","journal-title":"Biophys J"},{"key":"pcbi.1012727.ref007","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1477-5751-5-16","article-title":"Searching for plasticity in dissociated cortical cultures on multi-electrode arrays","volume":"5","author":"DA Wagenaar","year":"2006","journal-title":"J Negat Results Biomed"},{"key":"pcbi.1012727.ref008","doi-asserted-by":"crossref","first-page":"115591","DOI":"10.1016\/j.bios.2023.115591","article-title":"Investigation of the input-output relationship of engineered neural networks using high-density microelectrode arrays","volume":"239","author":"J Duru","year":"2023","journal-title":"Biosens Bioelectron"},{"issue":"5","key":"pcbi.1012727.ref009","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1152\/jn.00264.2005","article-title":"Signal propagation along unidimensional neuronal networks","volume":"94","author":"O Feinerman","year":"2005","journal-title":"J Neurophysiol"},{"issue":"17","key":"pcbi.1012727.ref010","doi-asserted-by":"crossref","first-page":"4526","DOI":"10.1523\/JNEUROSCI.4692-05.2006","article-title":"Transport of information along unidimensional layered networks of dissociated hippocampal neurons and implications for rate coding","volume":"26","author":"O Feinerman","year":"2006","journal-title":"J Neurosci"},{"issue":"11","key":"pcbi.1012727.ref011","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.aau4914","article-title":"Impact of modular organization on dynamical richness in cortical networks","volume":"4","author":"H Yamamoto","year":"2018","journal-title":"Sci Adv"},{"issue":"34","key":"pcbi.1012727.ref012","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.ade1755","article-title":"Modular architecture facilitates noise-driven control of synchrony in neuronal networks","volume":"9","author":"H Yamamoto","year":"2023","journal-title":"Sci Adv"},{"issue":"2","key":"pcbi.1012727.ref013","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/j.stemcr.2018.12.011","article-title":"Patient-specific iPSC-derived astrocytes contribute to non-cell-autonomous neurodegeneration in Parkinson\u2019s Disease","volume":"12","author":"A di Domenico","year":"2019","journal-title":"Stem Cell Reports"},{"issue":"3","key":"pcbi.1012727.ref014","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1523\/JNEUROSCI.4209-04.2005","article-title":"Controlling bursting in cortical cultures with closed-loop multi-electrode stimulation","volume":"25","author":"DA Wagenaar","year":"2005","journal-title":"J Neurosci"},{"issue":"3","key":"pcbi.1012727.ref015","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1088\/1741-2560\/5\/3\/004","article-title":"Spatio-temporal electrical stimuli shape behavior of an embodied cortical network in a goal-directed learning task","volume":"5","author":"DJ Bakkum","year":"2008","journal-title":"J Neural Eng"},{"issue":"23","key":"pcbi.1012727.ref016","doi-asserted-by":"crossref","first-page":"3952","DOI":"10.1016\/j.neuron.2022.09.001","article-title":"In vitro neurons learn and exhibit sentience when embodied in a simulated game-world","volume":"110","author":"BJ Kagan","year":"2022","journal-title":"Neuron"},{"issue":"22","key":"pcbi.1012727.ref017","doi-asserted-by":"crossref","first-page":"8782","DOI":"10.1523\/JNEUROSCI.21-22-08782.2001","article-title":"Learning in networks of cortical neurons","volume":"21","author":"G Shahaf","year":"2001","journal-title":"J Neurosci"},{"key":"pcbi.1012727.ref018","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.physrep.2007.02.014","article-title":"The physics of living neural networks","volume":"449","author":"J Eckmann","year":"2007","journal-title":"Physics Reports"},{"key":"pcbi.1012727.ref019","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0304-3940(96)12448-4","article-title":"Spontaneous periodic synchronized bursting during formation of mature patterns of connections in cortical cultures","volume":"206","author":"H Kamioka","year":"1996","journal-title":"Neurosci Lett"},{"issue":"10","key":"pcbi.1012727.ref020","doi-asserted-by":"crossref","first-page":"6834","DOI":"10.1523\/JNEUROSCI.15-10-06834.1995","article-title":"The mechanisms of generation and propagation of synchronized bursting in developing networks of cortical neurons","volume":"15","author":"E Maeda","year":"1995","journal-title":"J Neurosci"},{"issue":"7","key":"pcbi.1012727.ref021","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1005672","article-title":"Recurrently connected and localized neuronal communities initiate coordinated spontaneous activity in neuronal networks","volume":"13","author":"D Lonardoni","year":"2017","journal-title":"PLoS Comput Biol"},{"issue":"6","key":"pcbi.1012727.ref022","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S0166-2236(00)01813-0","article-title":"Developing networks play a similar melody","volume":"24","author":"Y Ben-Ari","year":"2001","journal-title":"Trends Neurosci"},{"issue":"5","key":"pcbi.1012727.ref023","doi-asserted-by":"crossref","first-page":"2196","DOI":"10.1152\/jn.00316.2002","article-title":"Spontaneous development of synchronous oscillatory activity during maturation of cortical networks in vitro","volume":"88","author":"T Opitz","year":"2002","journal-title":"J Neurophysiol"},{"key":"pcbi.1012727.ref024","doi-asserted-by":"crossref","first-page":"40","DOI":"10.3389\/fncir.2016.00040","article-title":"Spontaneous neuronal activity in developing neocortical networks: from single cells to large-scale interactions","volume":"10","author":"HJ Luhmann","year":"2016","journal-title":"Front Neural Circuits"},{"issue":"1","key":"pcbi.1012727.ref025","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/BF00228885","article-title":"Development in the absence of spontaneous bioelectric activity results in increased stereotyped burst firing in cultures of dissociated cerebral cortex","volume":"79","author":"GJ Ramakers","year":"1990","journal-title":"Exp Brain Res"},{"key":"pcbi.1012727.ref026","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/1471-2202-7-11","article-title":"An extremely rich repertoire of bursting patterns during the development of cortical cultures","volume":"7","author":"DA Wagenaar","year":"2006","journal-title":"BMC Neurosci"},{"issue":"2","key":"pcbi.1012727.ref027","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0168-0102(93)90076-3","article-title":"Formation and maturation of synapses in primary cultures of rat cerebral cortical cells: an electron microscopic study","volume":"16","author":"M Ichikawa","year":"1993","journal-title":"Neurosci Res"},{"issue":"8","key":"pcbi.1012727.ref028","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1111\/j.1460-9568.2010.07383.x","article-title":"Self-organization of repetitive spike patterns in developing neuronal networks in vitro","volume":"32","author":"J-J Sun","year":"2010","journal-title":"Eur J Neurosci"},{"issue":"4","key":"pcbi.1012727.ref029","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1002\/eej.10216","article-title":"Continuous monitoring of developmental activity changes in cultured cortical networks","volume":"145","author":"Y Mukai","year":"2003","journal-title":"Electrical Engineering Japan"},{"issue":"11","key":"pcbi.1012727.ref030","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1109\/TBME.2004.827936","article-title":"Long-term characterization of firing dynamics of spontaneous bursts in cultured neural networks","volume":"51","author":"J van Pelt","year":"2004","journal-title":"IEEE Trans Biomed Eng"},{"issue":"13","key":"pcbi.1012727.ref031","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1002\/dneu.20557","article-title":"Coemergence of regularity and complexity during neural network development","volume":"67","author":"E Fuchs","year":"2007","journal-title":"Dev Neurobiol"},{"key":"pcbi.1012727.ref032","doi-asserted-by":"crossref","first-page":"051907","DOI":"10.1103\/PhysRevE.73.051907","article-title":"Persistent dynamic attractors in activity patterns of cultured neuronal networks","volume":"73","author":"DA Wagenaar","year":"2006","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys"},{"key":"pcbi.1012727.ref033","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.neulet.2003.12.062","article-title":"Longterm stability and developmental changes in spontaneous network burst firing patterns in dissociated rat cerebral cortex cell cultures on multielectrode arrays","volume":"361","author":"J Van Pelt","year":"2004","journal-title":"Neurosci Lett"},{"issue":"8","key":"pcbi.1012727.ref034","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41583-024-00824-y","article-title":"Network state transitions during cortical development","volume":"25","author":"MW Wu","year":"2024","journal-title":"Nat Rev Neurosci"},{"issue":"7","key":"pcbi.1012727.ref035","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.tins.2006.05.007","article-title":"Early patterns of electrical activity in the developing cerebral cortex of humans and rodents","volume":"29","author":"R Khazipov","year":"2006","journal-title":"Trends Neurosci"},{"issue":"1","key":"pcbi.1012727.ref036","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/nrn2759","article-title":"Mechanisms underlying spontaneous patterned activity in developing neural circuits","volume":"11","author":"AG Blankenship","year":"2010","journal-title":"Nat Rev Neurosci"},{"key":"pcbi.1012727.ref037","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.conb.2017.07.004","article-title":"Understanding neural circuit development through theory and models","volume":"46","author":"LM Richter","year":"2017","journal-title":"Curr Opin Neurobiol"},{"issue":"3","key":"pcbi.1012727.ref038","article-title":"Homeostatic plasticity and external input shape neural network dynamics","volume":"8","author":"J Zierenberg","year":"2018","journal-title":"Phys Rev X"},{"issue":"7","key":"pcbi.1012727.ref039","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1038\/nrn3963","article-title":"Rethinking segregation and integration: contributions of whole-brain modelling","volume":"16","author":"G Deco","year":"2015","journal-title":"Nat Rev Neurosci"},{"issue":"9","key":"pcbi.1012727.ref040","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0107400","article-title":"Emergence of bursting activity in connected neuronal sub-populations","volume":"9","author":"M Bisio","year":"2014","journal-title":"PLoS One"},{"key":"pcbi.1012727.ref041","first-page":"32","article-title":"An in vitro method to manipulate the direction and functional strength between neural populations","volume":"9","author":"L Pan","year":"2015","journal-title":"Front Neural Circuits"},{"key":"pcbi.1012727.ref042","doi-asserted-by":"crossref","first-page":"10","DOI":"10.3389\/fneng.2011.00010","article-title":"Engineered neuronal circuits: a new platform for studying the role of modular topology","volume":"4","author":"M Shein-Idelson","year":"2011","journal-title":"Front Neuroeng"},{"key":"pcbi.1012727.ref043","doi-asserted-by":"crossref","first-page":"106967","DOI":"10.1016\/j.neunet.2024.106967","article-title":"Directional intermodular coupling enriches functional complexity in biological neuronal networks","volume":"184","author":"N Monma","year":"2025","journal-title":"Neural Netw"},{"key":"pcbi.1012727.ref044"},{"issue":"14","key":"pcbi.1012727.ref045","doi-asserted-by":"crossref","first-page":"3972","DOI":"10.1523\/JNEUROSCI.2552-16.2017","article-title":"Mesoscale architecture shapes initiation and richness of spontaneous network activity","volume":"37","author":"S Okujeni","year":"2017","journal-title":"J Neurosci"},{"issue":"14","key":"pcbi.1012727.ref046","doi-asserted-by":"crossref","first-page":"2515","DOI":"10.1523\/JNEUROSCI.1420-22.2023","article-title":"Structural modularity tunes mesoscale criticality in biological neuronal networks","volume":"43","author":"S Okujeni","year":"2023","journal-title":"J Neurosci"},{"key":"pcbi.1012727.ref047","unstructured":"Herna\u00e1ndez-Navarro L. Theoretical and experimental approaches for the initiation and propagation of activity in spatially embedded neuronal cultures. University of Barcelona; 2018."},{"issue":"9","key":"pcbi.1012727.ref048","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1038\/nphys2686","article-title":"Noise focusing and the emergence of coherent activity in neuronal cultures","volume":"9","author":"JG Orlandi","year":"2013","journal-title":"Nature Phys"},{"issue":"2","key":"pcbi.1012727.ref049","doi-asserted-by":"crossref","DOI":"10.1103\/PhysRevResearch.3.023133","article-title":"Noise-driven amplification mechanisms governing the emergence of coherent extreme events in excitable systems","volume":"3","author":"L Hern\u00e1ndez-Navarro","year":"2021","journal-title":"Phys Rev Research"},{"key":"pcbi.1012727.ref050","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.neunet.2018.02.016","article-title":"Connectivity inference from neural recording data: challenges, mathematical bases and research directions","volume":"102","author":"I Magrans de Abril","year":"2018","journal-title":"Neural Netw"},{"issue":"12","key":"pcbi.1012727.ref051","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.2216030120","article-title":"Network inference from short, noisy, low time-resolution, partial measurements: Application to C. elegans neuronal calcium dynamics","volume":"120","author":"A Banerjee","year":"2023","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"pcbi.1012727.ref052","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1103\/PhysRevLett.85.461","article-title":"Measuring information transfer","volume":"85","author":"T Schreiber","year":"2000","journal-title":"Phys Rev Lett"},{"issue":"8","key":"pcbi.1012727.ref053","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1002653","article-title":"Model-free reconstruction of excitatory neuronal connectivity from calcium imaging signals","volume":"8","author":"O Stetter","year":"2012","journal-title":"PLoS Comput Biol"},{"issue":"6","key":"pcbi.1012727.ref054","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0098842","article-title":"Transfer entropy reconstruction and labeling of neuronal connections from simulated calcium imaging","volume":"9","author":"JG Orlandi","year":"2014","journal-title":"PLoS One"},{"issue":"10","key":"pcbi.1012727.ref055","doi-asserted-by":"crossref","DOI":"10.1088\/1742-5468\/2008\/10\/P10008","article-title":"Fast unfolding of communities in large networks","volume":"2008","author":"VD Blondel","year":"2008","journal-title":"J Stat Mech"},{"issue":"5","key":"pcbi.1012727.ref056","doi-asserted-by":"crossref","first-page":"053139","DOI":"10.1063\/5.0201454","article-title":"Integrated information decomposition unveils major structural traits of in silico and in vitro neuronal networks","volume":"34","author":"G Menesse","year":"2024","journal-title":"Chaos"},{"key":"pcbi.1012727.ref057","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1038\/81453","article-title":"Synaptic plasticity: taming the beast","author":"LF Abbott","year":"2000","journal-title":"Nat Neurosci"},{"issue":"7","key":"pcbi.1012727.ref058","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.tins.2005.05.006","article-title":"Neurogeometry and potential synaptic connectivity","volume":"28","author":"A Stepanyants","year":"2005","journal-title":"Trends Neurosci"},{"key":"pcbi.1012727.ref059","doi-asserted-by":"crossref","first-page":"160","DOI":"10.3389\/fncom.2013.00160","article-title":"Estimating neuronal connectivity from axonal and dendritic density fields","volume":"7","author":"J van Pelt","year":"2013","journal-title":"Front Comput Neurosci"},{"issue":"42","key":"pcbi.1012727.ref060","article-title":"Statistical connectivity provides a sufficient foundation for specific functional connectivity in neocortical neural microcircuits","volume":"109","author":"SL Hill","year":"2012","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"30","key":"pcbi.1012727.ref061","doi-asserted-by":"crossref","first-page":"12536","DOI":"10.1073\/pnas.0901530106","article-title":"Maximization of the connectivity repertoire as a statistical principle governing the shapes of dendritic arbors","volume":"106","author":"Q Wen","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pcbi.1012727.ref062","doi-asserted-by":"crossref","first-page":"2314","DOI":"10.1152\/jn.00969.2010","article-title":"Network bursts in hippocampal microcultures are terminated by exhaustion of vesicle pools","volume":"106","author":"D Cohen","year":"2011","journal-title":"J Neurophysiol"},{"issue":"3","key":"pcbi.1012727.ref063","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1007\/s12021-009-9052-3","article-title":"NETMORPH: a framework for the stochastic generation of large scale neuronal networks with realistic neuron morphologies","volume":"7","author":"RA Koene","year":"2009","journal-title":"Neuroinformatics"},{"issue":"1","key":"pcbi.1012727.ref064","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s10827-009-0193-z","article-title":"Models of cortical networks with long-range patchy projections","volume":"28","author":"N Voges","year":"2010","journal-title":"J Comput Neurosci"},{"key":"pcbi.1012727.ref065","doi-asserted-by":"crossref","unstructured":"Braitenberg V, Schuz A. Anatomy of the cortex: statistics and geometry. Springer-Verlag; 1991.","DOI":"10.1007\/978-3-662-02728-8"},{"issue":"5","key":"pcbi.1012727.ref066","doi-asserted-by":"crossref","DOI":"10.1088\/1741-2552\/acf78b","article-title":"Deepening the role of excitation\/inhibition balance in human iPSCs-derived neuronal networks coupled to MEAs during long-term development","volume":"20","author":"G Parodi","year":"2023","journal-title":"J Neural Eng"},{"issue":"11","key":"pcbi.1012727.ref067","doi-asserted-by":"crossref","first-page":"3004","DOI":"10.3390\/cells10113004","article-title":"Experimental epileptogenesis in a cell culture model of primary neurons from rat brain: a temporal multi-scale study","volume":"10","author":"J Jablonski","year":"2021","journal-title":"Cells"},{"issue":"1","key":"pcbi.1012727.ref068","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41531-021-00198-3","article-title":"Parkinson\u2019s disease patient-specific neuronal networks carrying the LRRK2 G2019S mutation unveil early functional alterations that predate neurodegeneration","volume":"7","author":"G Carola","year":"2021","journal-title":"NPJ Parkinsons Dis"},{"issue":"1","key":"pcbi.1012727.ref069","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1038\/s41598-019-41220-2","article-title":"Inhibition increases response variability and reduces stimulus discrimination in random networks of cortical neurons","volume":"9","author":"N Haroush","year":"2019","journal-title":"Sci Rep"},{"issue":"6","key":"pcbi.1012727.ref070","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1109\/TNN.2003.820440","article-title":"Simple model of spiking neurons","volume":"14","author":"EM Izhikevich","year":"2003","journal-title":"IEEE Trans Neural Netw"},{"issue":"3","key":"pcbi.1012727.ref071","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1007\/s10827-008-0123-5","article-title":"Slow and fast pulses in 1-D cultures of excitatory neurons","volume":"26","author":"E Alvarez-Lacalle","year":"2009","journal-title":"J Comput Neurosci"},{"issue":"1","key":"pcbi.1012727.ref072","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1162\/neco.1994.6.1.14","article-title":"An efficient method for computing synaptic conductances based on a kinetic model of receptor binding","volume":"6","author":"A Destexhe","year":"1994","journal-title":"Neural Computation"},{"key":"pcbi.1012727.ref073","doi-asserted-by":"crossref","first-page":"38424","DOI":"10.1038\/srep38424","article-title":"Functional complexity emerging from anatomical constraints in the brain: the significance of network modularity and rich-clubs","volume":"6","author":"G Zamora-L\u00f3pez","year":"2016","journal-title":"Sci Rep"},{"key":"pcbi.1012727.ref074","unstructured":"Inc TM. MATLAB version: 9.13.0 (R2022b). MathWorks - Makers of MATLAB and Simulink. 2022. https:\/\/www.mathworks.com"},{"key":"pcbi.1012727.ref075","doi-asserted-by":"crossref","first-page":"056131","DOI":"10.1103\/PhysRevE.70.056131","article-title":"Analysis of weighted networks","volume":"70","author":"MEJ Newman","year":"2004","journal-title":"Phys Rev E Stat Nonlin Soft Matter Phys"},{"issue":"1","key":"pcbi.1012727.ref076","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1038\/s41598-019-41695-z","article-title":"From Louvain to Leiden: guaranteeing well-connected communities","volume":"9","author":"VA Traag","year":"2019","journal-title":"Sci Rep"},{"issue":"8","key":"pcbi.1012727.ref077","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pcbi.1000456","article-title":"Towards reproducible descriptions of neuronal network models","volume":"5","author":"E Nordlie","year":"2009","journal-title":"PLoS Comput Biol"}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1012727","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012727","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T19:00:57Z","timestamp":1763060457000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1012727"}},"subtitle":[],"editor":[{"given":"Matthias Helge","family":"Hennig","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2025,11,6]]},"references-count":77,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1012727","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,6]]}}}