{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T11:22:32Z","timestamp":1767180152534,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013765","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000}}],"reference-count":67,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CNRS, Agence Nationale de la Recherch"},{"name":"Human Brain Project","award":["H2020-94553"],"award-info":[{"award-number":["H2020-94553"]}]},{"name":"Virtual Brain Twin Model","award":["01137289"],"award-info":[{"award-number":["01137289"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>The activity of neurons in the central nervous system changes drastically across different states like asleep or awake, attentive or drowsy, behaving or resting. Neuromodulation supports these changes by altering neuronal excitability. Much work has been devoted to understanding the effects of neuromodulators on various neurons. However, we still lack a cohesive picture of how neuromodulation affects neuronal dynamics. Here, we provide an analytical framework to characterise neuromodulation.<\/jats:p>\n                  <jats:p>First, we analyse electrophysiological data from published papers and extract features for seven types of neurons from five areas of the human and rodent central nervous system, under the effect of five neuromodulators. Second, we describe this data using the widespread, simple, yet biologically accurate, Adaptive Exponential Integrate-and-Fire model (AdEx). Third, we use a dimensionality reduction technique to study the parameter space of the control and neuromodulated conditions. Fourth, we examine the dynamics of each neuromodulator through bifurcation and phase-plane analyses.<\/jats:p>\n                  <jats:p>Our analyses revealed that: (i) different neuromodulators remap the parameters space of neurons into non-overlapping clusters, (ii) changes in electrophysiological properties induced by neuromodulators can be explained by transitions between dynamical regimes in the excitability landscape of neurons, and (iii) there are only two distinct neuromodulatory effects: \u201cswitching\u201d \u2013 changing the spiking behaviour \u2013 and \u201cscaling\u201d \u2013 strengthening or weakening an existing behaviour. Leveraging this framework, we estimated the effect of neuromodulation in one species using data from another species.This study provides an integrative perspective on neuromodulation, offering experimenters and theoreticians a compact description of its impact on neuronal activity. The open-source Python-based workflow is modular and readily applicable to other datasets.<\/jats:p>","DOI":"10.1371\/journal.pcbi.1013765","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T18:51:26Z","timestamp":1764615086000},"page":"e1013765","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["A unified model library maps how neuromodulation reshapes the excitability landscape of neurons across the brain"],"prefix":"10.1371","volume":"21","author":[{"given":"Domenico","family":"Guarino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8210-8709","authenticated-orcid":true,"given":"Ilaria","family":"Carannante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alain","family":"Destexhe","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"issue":"1","key":"pcbi.1013765.ref001","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neuron.2012.09.010","article-title":"Neuromodulation of neuronal circuits: Back to the future","volume":"76","author":"E Marder","year":"2012","journal-title":"Neuron."},{"key":"pcbi.1013765.ref002","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.conb.2014.05.003","article-title":"Neuromodulation of neurons and synapses","volume":"29","author":"F Nadim","year":"2014","journal-title":"Curr Opin Neurobiol."},{"key":"pcbi.1013765.ref003","doi-asserted-by":"crossref","first-page":"278","DOI":"10.3389\/fncel.2020.00278","article-title":"Neuromodulation of glial function during neurodegeneration","volume":"14","author":"R Stevenson","year":"2020","journal-title":"Front Cell Neurosci."},{"key":"pcbi.1013765.ref004","unstructured":"Kaczmarek LK, Levitan IB. <refbooktitle>Neuromodulation: The biochemical control of neuronal excitability<\/refbooktitle>. New York: Oxford University Press; 1987."},{"key":"pcbi.1013765.ref005","unstructured":"Hille B. <refbooktitle>Ion channels of excitable membranes<\/refbooktitle>. 3rd ed. Sunderland (MA): Sinauer Associates; 2001."},{"key":"pcbi.1013765.ref006","unstructured":"Epelbaum J. <refbooktitle>Neuropeptides et neurom\u00e9diateurs. Paris: Sandoz; Ed. 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Haas","year":"1983","journal-title":"Nature."},{"issue":"10","key":"pcbi.1013765.ref019","doi-asserted-by":"crossref","first-page":"3188","DOI":"10.1523\/JNEUROSCI.11-10-03188.1991","article-title":"Modulation of neuronal firing mode in cat and guinea pig LGNd by histamine: Possible cellular mechanisms of histaminergic control of arousal","volume":"11","author":"DA McCormick","year":"1991","journal-title":"J Neurosci."},{"issue":"11","key":"pcbi.1013765.ref020","doi-asserted-by":"crossref","first-page":"1747","DOI":"10.1111\/j.1460-9568.2011.07893.x","article-title":"The role of cortical and hypothalamic histamine-3 receptors in the modulation of central histamine neurotransmission: An in vivo electrophysiology and microdialysis study","volume":"34","author":"G Flik","year":"2011","journal-title":"Eur J Neurosci."},{"key":"pcbi.1013765.ref021","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/S0079-6123(08)63817-0","article-title":"Actions of norepinephrine in the cerebral cortex and thalamus: Implications for function of the central noradrenergic system","volume":"88","author":"DA McCormick","year":"1991","journal-title":"Prog Brain Res."},{"issue":"3","key":"pcbi.1013765.ref022","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/cercor\/bhg128","article-title":"Co-expression and in vivo interaction of serotonin1A and serotonin2A receptors in pyramidal neurons of prefrontal cortex","volume":"14","author":"M Amarg\u00f3s-Bosch","year":"2004","journal-title":"Cereb Cortex."},{"issue":"1","key":"pcbi.1013765.ref023","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1007\/s00429-014-0924-4","article-title":"Conditional anterograde tracing reveals distinct targeting of individual serotonin cell groups (B5-B9) to the forebrain and brainstem","volume":"221","author":"A Muzerelle","year":"2016","journal-title":"Brain Struct Funct."},{"key":"pcbi.1013765.ref024","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/0006-8993(85)91524-0","article-title":"The frequency and distribution of medium-sized neurons with indented nuclei in the primate and rodent neostriatum","volume":"327","author":"GA Graveland","year":"1985","journal-title":"Brain Res."},{"key":"pcbi.1013765.ref025","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1146\/annurev-neuro-061010-113641","article-title":"Modulation of striatal projection systems by dopamine","volume":"34","author":"CR Gerfen","year":"2011","journal-title":"Annu Rev Neurosci."},{"issue":"3","key":"pcbi.1013765.ref026","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0057054","article-title":"Membrane properties of striatal direct and indirect pathway neurons in mouse and rat slices and their modulation by dopamine","volume":"8","author":"H Planert","year":"2013","journal-title":"PLoS 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Carver","year":"2019","journal-title":"J Neurosci."},{"issue":"2","key":"pcbi.1013765.ref030","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/0306-4522(90)90140-Y","article-title":"Effects of histamine on dentate granule cells in vitro","volume":"34","author":"RW Greene","year":"1990","journal-title":"Neuroscience."},{"issue":"2","key":"pcbi.1013765.ref031","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/0304-3940(87)90628-8","article-title":"Noradrenaline blocks potassium conductance in rat dentate granule cells in vitro","volume":"78","author":"HL Haas","year":"1987","journal-title":"Neurosci Lett."},{"issue":"8","key":"pcbi.1013765.ref032","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1111\/j.1476-5381.2009.00111.x","article-title":"Neural KCNQ (Kv7) channels","volume":"156","author":"DA Brown","year":"2009","journal-title":"Br J Pharmacol."},{"issue":"3","key":"pcbi.1013765.ref033","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.neuropharm.2006.03.030","article-title":"Modulation of thalamic neuron excitability by orexins","volume":"51","author":"G Govindaiah","year":"2006","journal-title":"Neuropharmacology."},{"issue":"1","key":"pcbi.1013765.ref034","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/0306-4522(90)90225-S","article-title":"Functional implications of burst firing and single spike activity in lateral geniculate relay neurons","volume":"39","author":"DA McCormick","year":"1990","journal-title":"Neuroscience."},{"key":"pcbi.1013765.ref035","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1113\/jphysiol.1987.sp016774","article-title":"Actions of acetylcholine in the guinea-pig and cat medial and lateral geniculate nuclei, in vitro","volume":"392","author":"DA McCormick","year":"1987","journal-title":"J Physiol."},{"issue":"4","key":"pcbi.1013765.ref036","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1016\/0013-4694(49)90219-9","article-title":"Brain stem reticular formation and activation of the EEG","volume":"1","author":"G Moruzzi","year":"1949","journal-title":"Electroencephalogr Clin Neurophysiol."},{"issue":"8","key":"pcbi.1013765.ref037","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1523\/JNEUROSCI.10-08-02541.1990","article-title":"Neuronal activities in brain-stem cholinergic nuclei related to tonic activation processes in thalamocortical systems","volume":"10","author":"M Steriade","year":"1990","journal-title":"J Neurosci."},{"issue":"6","key":"pcbi.1013765.ref038","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/0166-2236(89)90125-2","article-title":"Cholinergic and noradrenergic modulation of thalamocortical processing","volume":"12","author":"DA McCormick","year":"1989","journal-title":"Trends Neurosci."},{"issue":"2","key":"pcbi.1013765.ref039","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0306-4522(95)00009-8","article-title":"Corticothalamic projections from the primary visual cortex in rats: A single fiber study using biocytin as an anterograde tracer","volume":"66","author":"J Bourassa","year":"1995","journal-title":"Neuroscience."},{"issue":"4","key":"pcbi.1013765.ref040","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1002\/cne.903360402","article-title":"Branching projections from mesopontine nuclei to the nucleus reticularis and related thalamic nuclei: A double labelling study in the rat","volume":"336","author":"R Spreafico","year":"1993","journal-title":"J Comp Neurol."},{"issue":"6052","key":"pcbi.1013765.ref041","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/319402a0","article-title":"Acetylcholine induces burst firing in thalamic reticular neurones by activating a potassium conductance","volume":"319","author":"DA McCormick","year":"1986","journal-title":"Nature."},{"issue":"1","key":"pcbi.1013765.ref042","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1152\/jn.00492.2018","article-title":"Serotonin regulates dynamics of cerebellar granule cell activity by modulating tonic inhibition","volume":"121","author":"E Fleming","year":"2019","journal-title":"J Neurophysiol."},{"key":"pcbi.1013765.ref043","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1113\/jphysiol.1996.sp021224","article-title":"A non-inactivating K+ current sensitive to muscarinic receptor activation in rat cultured cerebellar granule neurons","author":"CS Watkins","year":"1996","journal-title":"J Physiol."},{"issue":"2","key":"pcbi.1013765.ref044","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1038\/sj.npp.1300829","article-title":"Dopamine D1 and D4 receptor subtypes differentially modulate recurrent excitatory synapses in prefrontal cortical pyramidal neurons","volume":"31","author":"S-P Onn","year":"2006","journal-title":"Neuropsychopharmacology."},{"issue":"4","key":"pcbi.1013765.ref045","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.4249\/scholarpedia.1430","article-title":"NEST (NEural simulation tool)","volume":"2","author":"M-O Gewaltig","year":"2007","journal-title":"Scholarpedia."},{"key":"pcbi.1013765.ref046","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.47314","article-title":"Brian 2, an intuitive and efficient neural simulator","volume":"8","author":"M Stimberg","year":"2019","journal-title":"Elife."},{"key":"pcbi.1013765.ref047","unstructured":"Rohatgi A. WebPlotDigitizer. https:\/\/automeris.io."},{"key":"pcbi.1013765.ref048","article-title":"The role of the thalamus in vigilance and epileptogenic mechanisms","author":"G Avanzini","year":"2000","journal-title":"Clin Neurophysiol."},{"issue":"6","key":"pcbi.1013765.ref049","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.3390\/molecules27061816","article-title":"Role of cholinergic signaling in Alzheimer\u2019s disease","volume":"27","author":"Z-R Chen","year":"2022","journal-title":"Molecules."},{"key":"pcbi.1013765.ref050","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.cca.2021.08.009","article-title":"Dopamine in Parkinson\u2019s disease","volume":"522","author":"S Latif","year":"2021","journal-title":"Clin Chim Acta."},{"issue":"4","key":"pcbi.1013765.ref051","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/sj.mp.4001949","article-title":"Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: A meta-analysis of monoamine depletion studies","volume":"12","author":"HG Ruh\u00e9","year":"2007","journal-title":"Mol Psychiatry."},{"key":"pcbi.1013765.ref052","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1002\/1520-6394(2000)12:1+<2::AID-DA2>3.0.CO;2-4","article-title":"Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders","author":"KJ Ressler","year":"2000","journal-title":"Depress Anxiety."},{"issue":"8","key":"pcbi.1013765.ref053","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/nrn.2016.57","article-title":"Dysregulation of the dopamine system in the pathophysiology of schizophrenia and depression","volume":"17","author":"AA Grace","year":"2016","journal-title":"Nat Rev Neurosci."},{"issue":"5","key":"pcbi.1013765.ref054","doi-asserted-by":"crossref","first-page":"2635","DOI":"10.1137\/070709359","article-title":"Constructing sobol sequences with better two-dimensional projections","volume":"30","author":"S Joe","year":"2008","journal-title":"SIAM J Sci Comput."},{"key":"pcbi.1013765.ref055","doi-asserted-by":"crossref","unstructured":"Kluyver T, Ragan-Kelley B, P\u00e9rez F, Granger B, Bussonnier M, Frederic J, et al. Jupyter notebooks\u2014A publishing format for reproducible computational workflows. <refbooktitle>Positioning and power in academic publishing: Players, agents and agendas<\/refbooktitle>. IOS Press; 2016. p. 87\u201390.","DOI":"10.3233\/978-1-61499-649-1-87"},{"issue":"7825","key":"pcbi.1013765.ref056","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","article-title":"Array programming with NumPy","volume":"585","author":"CR Harris","year":"2020","journal-title":"Nature."},{"issue":"3","key":"pcbi.1013765.ref057","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","article-title":"SciPy 1.0: Fundamental algorithms for scientific computing in Python","volume":"17","author":"P Virtanen","year":"2020","journal-title":"Nat Methods."},{"issue":"3","key":"pcbi.1013765.ref058","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1109\/MCSE.2007.55","article-title":"Matplotlib: A 2D graphics environment","volume":"9","author":"JD Hunter","year":"2007","journal-title":"Comput Sci Eng."},{"issue":"16","key":"pcbi.1013765.ref059","doi-asserted-by":"crossref","first-page":"4444","DOI":"10.1523\/JNEUROSCI.5602-05.2006","article-title":"Attentional modulation of thalamic reticular neurons","volume":"26","author":"K McAlonan","year":"2006","journal-title":"J Neurosci."},{"issue":"4","key":"pcbi.1013765.ref060","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1002\/cne.1389","article-title":"Synaptic targets of thalamic reticular nucleus terminals in the visual thalamus of the cat","volume":"440","author":"S Wang","year":"2001","journal-title":"J Comp Neurol."},{"key":"pcbi.1013765.ref061","first-page":"2825","article-title":"Scikit-learn: Machine learning in Python","volume":"12","author":"F Pedregosa","year":"2011","journal-title":"J Mach Learn Res."},{"issue":"1","key":"pcbi.1013765.ref062","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1523\/JNEUROSCI.21-01-00075.2001","article-title":"Cholinergic modulation of excitatory synaptic transmission in the CA3 area of the hippocampus","volume":"21","author":"KE Vogt","year":"2001","journal-title":"J Neurosci."},{"key":"pcbi.1013765.ref063","unstructured":"Jones EG. <refbooktitle>The thalamus<\/refbooktitle>. Springer Science & Business Media; 2012."},{"issue":"2","key":"pcbi.1013765.ref064","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1007\/s12311-011-0331-9","article-title":"Consensus paper: Roles of the cerebellum in motor control\u2014The diversity of ideas on cerebellar involvement in movement","volume":"11","author":"M Manto","year":"2012","journal-title":"Cerebellum."},{"key":"pcbi.1013765.ref065","article-title":"Diverse inhibitory projections from the cerebellar interposed nucleus","volume":"10","author":"EN Judd","year":"2021","journal-title":"Elife."},{"issue":"8","key":"pcbi.1013765.ref066","doi-asserted-by":"crossref","first-page":"3243","DOI":"10.1038\/s41380-022-01661-0","article-title":"The serotonin theory of depression: A systematic umbrella review of the evidence","volume":"28","author":"J Moncrieff","year":"2023","journal-title":"Mol Psychiatry."},{"issue":"8","key":"pcbi.1013765.ref067","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1038\/s41380-023-02095-y","article-title":"A leaky umbrella has little value: Evidence clearly indicates the serotonin system is implicated in depression","volume":"28","author":"S Jauhar","year":"2023","journal-title":"Mol Psychiatry."}],"updated-by":[{"DOI":"10.1371\/journal.pcbi.1013765","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000}}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013765","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T19:17:04Z","timestamp":1764962224000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1013765"}},"subtitle":[],"editor":[{"given":"Hermann","family":"Cuntz","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":67,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12,1]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1013765","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]}}}