{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:57:29Z","timestamp":1793332649760,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Leibniz Best Minds program","award":["J28\/2017"],"award-info":[{"award-number":["J28\/2017"]}]},{"name":"Center for Behavioral Brain Sciences through ERFE-program","award":["J28\/2017"],"award-info":[{"award-number":["J28\/2017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The Locus coeruleus (LC) modulates various neuronal circuits throughout the brain. Its unique architectural organization encompasses a net of axonal innervation that spans the entire brain, while its somatic core is highly compact. Recent research revealed an unexpected cellular input specificity within the nucleus that can give rise to various network states that either broadcast norepinephrine signals throughout the brain or pointedly modulate specific brain areas. Such adaptive input\u2013output functions likely surpass our existing network models that build upon a given synaptic wiring configuration between neurons. As the distances between noradrenergic neurons in the core of the LC are unusually small, neighboring neurons could theoretically impact each other via volume transmission of NE. We therefore set out to investigate if such interaction could be mediated through noradrenergic alpha2-receptors in a spiking neuron model of the LC. We validated our model of LC neurons through comparison with experimental patch-clamp data and identified key variables that impact alpha2-mediated inhibition of neighboring LC neurons. Our simulation confirmed a reliable autoinhibition of LC neurons after episodes of high neuronal activity that continue even after neuronal activity subsided. Additionally, dendro-somatic synapses inhibited spontaneous spiking in the somatic compartment of connected neurons in our model. We determined the exact position of hundreds of LC neurons in the mouse brain stem via a tissue clearing approach and, based on this, further determined that 25 percent of noradrenergic neurons have a neighboring LC neuron within less than a 25-micrometer radius. By modeling NE diffusion, we estimated that more than 15 percent of the alpha2-adrenergic receptors fraction can bind NE within such a diffusion radius. Our spiking neuron model of LC neurons predicts that repeated or long-lasting episodes of high neuronal activity induce partitioning of the gross LC network and reduce the spike rate in neighboring neurons at distances smaller than 25 \u03bcm. As these volume-mediating neighboring effects are challenging to test with the current methodology, our findings can guide future experimental approaches to test this phenomenon and its physiological consequences.<\/jats:p>","DOI":"10.3390\/brainsci12060728","type":"journal-article","created":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T12:48:31Z","timestamp":1654087711000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Spike-Dependent Dynamic Partitioning of the Locus Coeruleus Network through Noradrenergic Volume Release in a Simulation of the Nucleus Core"],"prefix":"10.3390","volume":"12","author":[{"given":"Shristi","family":"Baral","sequence":"first","affiliation":[{"name":"Research Group Neuromodulatory Networks, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany"},{"name":"Cognitive Biology, Faculty of Natural Sciences, Otto-von Guericke University, 39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Research Group Neuromodulatory Networks, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaushik","family":"More","sequence":"additional","affiliation":[{"name":"Research Group Neuromodulatory Networks, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomaz M. C.","family":"Fabrin","sequence":"additional","affiliation":[{"name":"Research Group Neuromodulatory Networks, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Braun","sequence":"additional","affiliation":[{"name":"Cognitive Biology, Faculty of Natural Sciences, Otto-von Guericke University, 39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Prigge","sequence":"additional","affiliation":[{"name":"Research Group Neuromodulatory Networks, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany"},{"name":"Center for Behavioral Brain Sciences, 39118 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1177\/0269881113490326","article-title":"Functional neuroanatomy of the central noradrenergic system","volume":"27","author":"Szabadi","year":"2013","journal-title":"J. Psychopharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1038\/nn.2682","article-title":"Tuning arousal with optogenetic modulation of locus coeruleus neurons","volume":"13","author":"Carter","year":"2010","journal-title":"Nat. Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e29808","DOI":"10.7554\/eLife.29808","article-title":"Functional dichotomy in spinal- vs prefrontal-projecting locus coeruleus modules splits descending noradrenergic analgesia from ascending aversion and anxiety in rats","volume":"6","author":"Hirschberg","year":"2017","journal-title":"eLife"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nature19325","article-title":"Locus coeruleus and dopaminergic consolidation of everyday memory","volume":"537","author":"Takeuchi","year":"2016","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.1038\/nn.4090","article-title":"Coordinated forms of noradrenergic plasticity in the locus coeruleus and primary auditory cortex","volume":"18","author":"Martins","year":"2015","journal-title":"Nat. Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/s41583-020-0360-9","article-title":"Locus coeruleus: A new look at the blue spot","volume":"21","author":"Poe","year":"2020","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Matos, S.C., Jego, S., Adamantidis, A., and S\u00e9gu\u00e9la, P. (2013). Norepinephrine drives persistent activity in prefrontal cortex via synergistic \u03b11 and \u03b12 adrenoceptors. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0066122"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0006-8993(77)90759-4","article-title":"Noradrenergic axon terminals in the cerebral cortex of rat. III. Topometric ultrastructural analysis","volume":"133","author":"Descarries","year":"1977","journal-title":"Brain Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1002\/cne.10156","article-title":"Noradrenergic innervation of the developing and mature visual and motor cortex of the rat brain: A light and electron microscopic immunocytochemical analysis","volume":"445","author":"Latsari","year":"2002","journal-title":"J. Comp. Neurol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1177\/29.2.7019303","article-title":"Ultrastructural demonstration of noradrenergic synapses in the rat central nervous system by dopamine-beta-hydroxylase immunocytochemistry","volume":"29","author":"Olschowka","year":"1981","journal-title":"J. Histochem. Cytochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/0006-8993(81)90843-X","article-title":"Ultrastructural immunocytochemical localization of tyrosine hydroxylase in the neostriatum","volume":"225","author":"Pickel","year":"1981","journal-title":"Brain Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4135","DOI":"10.1523\/JNEUROSCI.16-13-04135.1996","article-title":"Ultrastructural localization of the vesicular monoamine transporter-2 in midbrain dopaminergic neurons: Potential sites for somatodendritic storage and release of dopamine","volume":"16","author":"Nirenberg","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6816","DOI":"10.1073\/pnas.1320827111","article-title":"Heterogeneous organization of the locus coeruleus projections to prefrontal and motor cortices","volume":"111","author":"Chandler","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1038\/nn.4642","article-title":"Modular organization of the brainstem noradrenaline system coordinates opposing learning states","volume":"20","author":"Uematsu","year":"2017","journal-title":"Nat. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.brainresrev.2008.02.004","article-title":"Dopamine spillover after quantal release: Rethinking dopamine transmission in the nigrostriatal pathway","volume":"58","author":"Rice","year":"2008","journal-title":"Brain Res. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20140185","DOI":"10.1098\/rstb.2014.0185","article-title":"Somatodendritic dopamine release: Recent mechanistic insights","volume":"370","author":"Rice","year":"2015","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.tins.2004.03.011","article-title":"DAncing past the DAT at a DA synapse","volume":"27","author":"Cragg","year":"2004","journal-title":"Trends Neurosci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"5196","DOI":"10.1523\/JNEUROSCI.16-16-05196.1996","article-title":"Synchronous activity in locus coeruleus results from dendritic interactions in pericoerulear regions","volume":"16","author":"Ishimatsu","year":"1996","journal-title":"J. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0306-4522(93)90568-Z","article-title":"Dye-coupling among neurons of the rat locus coeruleus during postnatal development","volume":"56","author":"Christi","year":"1993","journal-title":"Neuroscience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3584","DOI":"10.1523\/JNEUROSCI.09-10-03584.1989","article-title":"Electrical coupling synchronizes subthreshold activity in locus coeruleus neurons in vitro from neonatal rats","volume":"9","author":"Christie","year":"1989","journal-title":"J. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Totah, N.K., Logothetis, N.K., and Eschenko, O. (2020). Synchronous spiking associated with high gamma oscillations in prefrontal cortex exerts top-down control over a 5Hz-rhythmic modulation of spiking in locus coeruleus. bioRxiv.","DOI":"10.1101\/2020.04.26.061085"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"7464","DOI":"10.1523\/JNEUROSCI.0973-20.2020","article-title":"Chronic environmental or genetic elevation of galanin in noradrenergic neurons confers stress resilience in mice","volume":"40","author":"Tillage","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.bbrc.2018.05.181","article-title":"Activation of galanin receptor 1 inhibits locus coeruleus neurons via GIRK channels","volume":"503","author":"Bai","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1113\/jphysiol.1979.sp012628","article-title":"Serotonergic innervation of the locus coeruleus from the dorsal raphe and its action on responses to noxious stimuli","volume":"286","author":"Segal","year":"1979","journal-title":"J. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/0006-8993(77)90083-X","article-title":"Evidence for norepinephrine-mediated collateral inhibition of locus coeruleus neurons","volume":"136","author":"Aghajanian","year":"1977","journal-title":"Brain Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S0301-0082(98)00039-2","article-title":"Release of neurotransmitters in the locus coeruleus","volume":"56","author":"Singewald","year":"1998","journal-title":"Prog. Neurobiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1007\/BF00178948","article-title":"In vivo release of catecholamines in the locus coeruleus","volume":"350","author":"Singewald","year":"1994","journal-title":"Naunyn-Schmiedebergs Arch. Exp. Pathol. Pharmakol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"9950","DOI":"10.1073\/pnas.94.18.9950","article-title":"Substitution of a mutant \u03b12a -adrenergic receptor via \u201chit and run\u201d gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo","volume":"94","author":"Lakhlani","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1111\/ejn.14553","article-title":"Axonal projection-specific differences in somatodendritic \u03b12 autoreceptor function in locus coeruleus neurons","volume":"50","author":"Fischer","year":"2019","journal-title":"Eur. J. Neurosci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/0006-8993(76)90207-9","article-title":"The locus coeruleus: A cytoarchitectonic, golgi and immunohistochemical study in the albino rat","volume":"110","author":"Swanson","year":"1976","journal-title":"Brain Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0006-8993(98)00266-2","article-title":"A2A-adrenergic receptors in the rat nucleus locus coeruleus: Subcellular localization in catecholaminergic dendrites, astrocytes, and presynaptic axon terminals","volume":"795","author":"Lee","year":"1998","journal-title":"Brain Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1017\/S1461145712000971","article-title":"Role of GIRK channels on the noradrenergic transmission in vivo: An electrophysiological and neurochemical study on GIRK2 mutant mice","volume":"16","author":"Torrecilla","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1152\/jn.1995.74.2.519","article-title":"Opioid inhibition in locus coeruleus","volume":"74","author":"Travagli","year":"1995","journal-title":"J. Neurophysiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2029","DOI":"10.1152\/jn.1996.75.5.2029","article-title":"Dendritic arbor of locus coeruleus neurons contributes to opioid inhibition","volume":"75","author":"Travagli","year":"1996","journal-title":"J. Neurophysiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4299","DOI":"10.1523\/JNEUROSCI.08-11-04299.1988","article-title":"Inward rectification of resting and opiate-activated potassium currents in rat locus coeruleus neurons","volume":"8","author":"Williams","year":"1988","journal-title":"J. Neurosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nrn2834","article-title":"Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease","volume":"11","author":"Slesinger","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3389\/fnmol.2012.00029","article-title":"Physiology of quantal norepinephrine release from somatodendritic sites of neurons in locus coeruleus","volume":"5","author":"Huang","year":"2012","journal-title":"Front. Mol. Neurosci."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1073\/pnas.0608897104","article-title":"Long latency of evoked quantal transmitter release from somata of locus coeruleus neurons in rat pontine slices","volume":"104","author":"Huang","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1073\/pnas.062716299","article-title":"Frequency-dependent synchrony in locus ceruleus: Role of electrotonic coupling","volume":"99","author":"Alvarez","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0079-6123(08)63806-6","article-title":"Synaptic potentials in locus coeruleus neurons in brain slices","volume":"88","author":"Williams","year":"1991","journal-title":"Prog. Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1002\/cbic.201900485","article-title":"Lamprey parapinopsin (\u201cUVLamP\u201d): A bistable uv-sensitive optogenetic switch for ultrafast control of gpcr pathways","volume":"21","author":"Eickelbeck","year":"2019","journal-title":"ChemBioChem"},{"key":"ref_42","unstructured":"Alan, A., Boulton, G.B.B., and Adams, R.N. (1995). Diffusion and ion shifts in the brain extracellular microenvironment and their relevance for voltammetric measurements. Voltammetric Methods in Brain Systems, Humana Press."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/0006-8993(84)90170-7","article-title":"Intrinsic regulation of locus coeruleus neurons: Electrophysiological evidence indicating a predominant role for autoinhibition","volume":"310","author":"Andrade","year":"1984","journal-title":"Brain Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/0306-4522(84)90265-3","article-title":"Membrane properties of rat locus coeruleus neurones","volume":"13","author":"Williams","year":"1984","journal-title":"Neuroscience"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1016\/j.neuron.2018.07.037","article-title":"The locus coeruleus is a complex and differentiated neuromodulatory system","volume":"99","author":"Totah","year":"2018","journal-title":"Neuron"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41593-018-0305-z","article-title":"Active control of arousal by a locus coeruleus GABAergic circuit","volume":"22","author":"Sur","year":"2019","journal-title":"Nat. Neurosci."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Jin, X., Li, S., Bondy, B., Zhong, W., Oginsky, M.F., Wu, Y., Johnson, C.M., Zhang, S., Cui, N., and Jiang, C. (2016). Identification of a group of GABAergic neurons in the dorsomedial area of the locus coeruleus. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0146470"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"4003","DOI":"10.1113\/JP279557","article-title":"Inhibitory interneurons regulate phasic activity of noradrenergic neurons in the mouse locus coeruleus and functional implications","volume":"598","author":"Kuo","year":"2020","journal-title":"J. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"14835","DOI":"10.1073\/pnas.1616515114","article-title":"Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory","volume":"113","author":"Kempadoo","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1111\/j.1365-2990.1985.tb00004.x","article-title":"A quantitative histological study of neuronal loss from the locus coeruleus of ageing mice","volume":"11","author":"Sturrock","year":"1985","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.jchemneu.2007.05.008","article-title":"Catecholaminergic neuronal loss in locus coeruleus of aged female dtg APP\/PS1 mice","volume":"34","author":"Mouton","year":"2007","journal-title":"J. Chem. Neuroanat."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"8451","DOI":"10.1523\/JNEUROSCI.17-21-08451.1997","article-title":"Reduced Levels of Norepinephrine Transporters in the Locus Coeruleus in Major Depression","volume":"17","author":"Klimek","year":"1997","journal-title":"J. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/1471-2377-11-88","article-title":"Enhanced catecholamine transporter binding in the locus coeruleus of patients with early Parkinson disease","volume":"11","author":"Isaias","year":"2011","journal-title":"BMC Neurol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7645","DOI":"10.1523\/JNEUROSCI.0166-14.2014","article-title":"The Timing of Dopamine- and Noradrenaline-mediated transmission reflects underlying differences in the extent of spillover and pooling","volume":"34","author":"Courtney","year":"2014","journal-title":"J. Neurosci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1021\/cn5000666","article-title":"A Novel restricted diffusion model of evoked dopamine","volume":"5","author":"Walters","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/cne.903360304","article-title":"Topographic organization of rat locus coeruleus and dorsal raphe nuclei: Distribution of cells projecting to visual system structures","volume":"336","author":"Waterhouse","year":"1993","journal-title":"J. Comp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/0306-4522(86)90155-7","article-title":"Efferent projections of nucleus locus coeruleus: Topographic organization of cells of origin demonstrated by three-dimensional reconstruction","volume":"18","author":"Loughlin","year":"1986","journal-title":"Neuroscience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0361-9230(82)90142-3","article-title":"Locus coeruleus projections to cortex: Topography, morphology and collateralization","volume":"9","author":"Loughlin","year":"1982","journal-title":"Brain Res. Bull."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1002\/cne.901870405","article-title":"Regional topography within noradrenergic locus coeruleus as revealed by retrograde transport of horseradish peroxidase","volume":"187","author":"Mason","year":"1979","journal-title":"J. Comp. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1038\/nature14600","article-title":"Viral-genetic tracing of the input\u2013output organization of a central noradrenaline circuit","volume":"524","author":"Schwarz","year":"2015","journal-title":"Nature"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/6\/728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:23:23Z","timestamp":1760138603000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/12\/6\/728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,1]]},"references-count":60,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["brainsci12060728"],"URL":"https:\/\/doi.org\/10.3390\/brainsci12060728","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.02.13.480256","asserted-by":"object"}]},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,1]]}}}