{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T02:10:12Z","timestamp":1790647812516,"version":"4.1.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T00:00:00Z","timestamp":1758585600000},"content-version":"vor","delay-in-days":22,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Forschungszentrum J\u00fclich GmbH"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Anat Sci Int"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Fine-scale transmission electron microscopy (TEM), focused ion beam scanning EM (FIB), and EM tomography have opened a new window on the synaptic organization of the normal, developing and pathologically altered brain in experimental animals. Progress in the human brain has been slower, due to technical challenges and the problem of tissue availability from donors that underwent epilepsy or tumor surgery. The present manuscript is in part an overview of the geometry of synaptic boutons in surgical biopsy samples taken from human temporal lobe neocortex (\u2018hTLN\u2019). Here, the number, size, and shape of active zones (the equivalent of functional neurotransmitter release sites) and the three functionally defined pools of synaptic vesicles were quantified, with comparisons to the same parameters in experimental animals. High-resolution TEM tomography further allowed new insights concerning the readily releasable pool of synaptic vesicles, one of the key structural elements in synaptic transmission and plasticity. The quantitative 3D models of synaptic boutons provide the basis for numerical and\/or Monte Carlo simulations of various signal cascades underlying synaptic transmission that at least in humans are still only partially accessible for experiment. In a second focus, we provide a step-by-step walk-through with illustrations of basic methodology for tissue preparation and analysis, for both TEM and FIB-SEM, including a thorough discussion of the main advantages and disadvantages of the several techniques and the particular challenge of working with human tissue.<\/jats:p>","DOI":"10.1007\/s12565-025-00900-y","type":"journal-article","created":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T13:16:49Z","timestamp":1758633409000},"page":"480-497","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The synaptic organization of the human temporal lobe neocortex by high-resolution transmission, focused ion beam scanning, and electron microscopic tomography"],"prefix":"10.1007","volume":"100","author":[{"given":"Astrid","family":"Rollenhagen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joachim H. R.","family":"L\u00fcbke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,23]]},"reference":[{"key":"900_CR1","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1016\/j.jns.2017.08.007","volume":"381","author":"C Allone","year":"2017","unstructured":"Allone C, Lo Buono V, Corallo F, Pisani LR, Pollicino P, Bramanti P, Marino S (2017) Neuroimaging and cognitive functions in temporal lobe epilepsy: a review of the literature. J Neurol Sci 381:7\u201315","journal-title":"J Neurol Sci"},{"key":"900_CR2","doi-asserted-by":"publisher","first-page":"14615","DOI":"10.1073\/pnas.0803652105","volume":"105","author":"L Alonso-Nanclares","year":"2008","unstructured":"Alonso-Nanclares L, Gonzalez-Soriano J, Rodriguez JR, DeFelipe J (2008) Gender differences in human cortical synaptic density. Proc Natl Acad Sci USA 105:14615\u201314619","journal-title":"Proc Natl Acad Sci USA"},{"key":"900_CR3","doi-asserted-by":"publisher","first-page":"2850","DOI":"10.1038\/s41467-023-38585-4","volume":"14","author":"V Bazinet","year":"2023","unstructured":"Bazinet V, Hansen JY, Vos de Wael R, Bernhardt BC, van den Heuvel MP, Misic B (2023) Assortative mixing in micro-architecturally annotated brain connectomes. Nat Commun 14:2850","journal-title":"Nat Commun"},{"key":"900_CR4","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhae180","author":"R Benavides-Piccione","year":"2024","unstructured":"Benavides-Piccione R, Blazquez-Llorca L, Kastanauskaite A, Fernaud-Espinosa I, Tapia-Gonzalez S, DeFelipe J (2024) Key morphological features of human pyramidal neurons. Cereb Cortex. https:\/\/doi.org\/10.1093\/cercor\/bhae180","journal-title":"Cereb Cortex"},{"key":"900_CR5","doi-asserted-by":"publisher","DOI":"10.3389\/fnhum.2013.00624","volume":"7","author":"BC Bernhardt","year":"2013","unstructured":"Bernhardt BC, Hong S, Bernasconi A, Bernasconi N (2013) Imaging structural and functional brain networks in temporal lobe epilepsy. Front Hum Neurosci 7:624","journal-title":"Front Hum Neurosci"},{"key":"900_CR6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.118993","volume":"252","author":"RF Betzel","year":"2022","unstructured":"Betzel RF, Cutts SA, Greenwell S, Faskowitz J, Sporns O (2022) Individualized event structure drives individual differences in whole-brain functional connectivity. Neuroimage 252:118993","journal-title":"Neuroimage"},{"key":"900_CR7","doi-asserted-by":"publisher","first-page":"995","DOI":"10.3233\/JAD-122038","volume":"34","author":"L Blazquez-Llorca","year":"2013","unstructured":"Blazquez-Llorca L, Merchan-Perez A, Rodriguez JR, Gascon J, DeFelipe J (2013) FIB\/SEM technology and Alzheimer\u2019s disease: three-dimensional analysis of human cortical synapses. J Alzheimers Dis 34:995\u20131013","journal-title":"J Alzheimers Dis"},{"key":"900_CR8","doi-asserted-by":"publisher","first-page":"2435","DOI":"10.1523\/JNEUROSCI.2557-16.2017","volume":"37","author":"R Bopp","year":"2017","unstructured":"Bopp R, Holler-Rickauer S, Martin KA, Schuhknecht GF (2017) An ultrastructural study of the thalamic input to layer 4 of primary motor and primary somatosensory cortex in the mouse. J Neurosci 37:2435\u20132448","journal-title":"J Neurosci"},{"key":"900_CR9","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/s41583-019-0212-7","volume":"20","author":"RL Buckner","year":"2019","unstructured":"Buckner RL, DiNicola LM (2019) The brain\u2019s default network: updated anatomy, physiology and evolving insights. Nat Rev Neurosci 20:593\u2013608","journal-title":"Nat Rev Neurosci"},{"key":"900_CR10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/0306-4522(89)90227-3","volume":"28","author":"EH Buhl","year":"1989","unstructured":"Buhl EH, L\u00fcbke J (1989) Intracellular lucifer yellow injection in fixed brain slices combined with retrograde tracing, light and electron microscopy. Neuroscience 28:3\u201316","journal-title":"Neuroscience"},{"key":"900_CR11","doi-asserted-by":"publisher","first-page":"4742","DOI":"10.1093\/cercor\/bhab120","volume":"31","author":"N Cano-Astorga","year":"2021","unstructured":"Cano-Astorga N, DeFelipe J, Alonso-Nanclares L (2021) Three-dimensional synaptic organization of layer III of the human temporal neocortex. Cereb Cortex 31:4742\u20134764","journal-title":"Cereb Cortex"},{"key":"900_CR12","doi-asserted-by":"publisher","first-page":"9691","DOI":"10.1093\/cercor\/bhad232","volume":"33","author":"N Cano-Astorga","year":"2023","unstructured":"Cano-Astorga N, Plaza-Alonso S, DeFelipe J, Alonso-Nanclares L (2023) 3D synaptic organization of layer III of the human anterior cingulate and temporopolar cortex. Cereb Cortex 33:9691\u20139708","journal-title":"Cereb Cortex"},{"key":"900_CR13","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhae312","author":"N Cano-Astorga","year":"2024","unstructured":"Cano-Astorga N, Plaza-Alonso S, DeFelipe J, Alonso-Nanclares L (2024) Volume electron microscopy analysis of synapses in primary regions of the human cerebral cortex. Cereb Cortex. https:\/\/doi.org\/10.1093\/cercor\/bhae312","journal-title":"Cereb Cortex"},{"key":"900_CR14","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1093\/cercor\/bhs048","volume":"23","author":"S Caspers","year":"2013","unstructured":"Caspers S, Schleicher A, Bacha-Trams M, Palomero-Gallagher N, Amunts K, Zilles K (2013) Organization of the human inferior parietal lobule based on receptor architectonics. Cereb Cortex 23:615\u2013628","journal-title":"Cereb Cortex"},{"key":"900_CR15","unstructured":"Deerinck TJ et al. (2010). NCMIR methods for 3D EM: A new protocol for preparation of biological specimens for serial block-face SEM. Microscopy Online."},{"key":"900_CR16","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2011.00029","volume":"5","author":"J DeFelipe","year":"2011","unstructured":"DeFelipe J (2011) The evolution of the brain, the human nature of cortical circuits, and intellectual creativity. Front Neuroanat 5:29","journal-title":"Front Neuroanat"},{"key":"900_CR17","doi-asserted-by":"publisher","first-page":"722","DOI":"10.1093\/cercor\/9.7.722","volume":"9","author":"J DeFelipe","year":"1999","unstructured":"DeFelipe J, Marco P, Busturia I, Merchan-Perez A (1999) Estimation of the number of synapses in the cerebral cortex: methodological considerations. Cereb Cortex 9:722\u2013732","journal-title":"Cereb Cortex"},{"key":"900_CR18","volume":"2","author":"A Denker","year":"2010","unstructured":"Denker A, Rizzoli SO (2010) Synaptic vesicle pools: an update. Front Synaptic Neurosci 2:135","journal-title":"Front Synaptic Neurosci"},{"key":"900_CR19","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0140-19.2019","author":"M Dominguez-Alvaro","year":"2019","unstructured":"Dominguez-Alvaro M, Montero-Crespo M, Blazquez-Llorca L, DeFelipe J, Alonso-Nanclares L (2019) 3D electron microscopy study of synaptic organization of the normal human transentorhinal cortex and its possible alterations in Alzheimer\u2019s disease. eNeuro. https:\/\/doi.org\/10.1523\/ENEURO.0140-19.2019","journal-title":"eNeuro"},{"key":"900_CR20","doi-asserted-by":"publisher","first-page":"410","DOI":"10.1093\/cercor\/bhaa233","volume":"31","author":"M Dominguez-Alvaro","year":"2021","unstructured":"Dominguez-Alvaro M, Montero-Crespo M, Blazquez-Llorca L, DeFelipe J, Alonso-Nanclares L (2021) 3D ultrastructural study of synapses in the human entorhinal cortex. Cereb Cortex 31:410\u2013425","journal-title":"Cereb Cortex"},{"key":"900_CR21","first-page":"838","volume":"26","author":"A Dufour","year":"2016","unstructured":"Dufour A, Rollenhagen A, S\u00e4tzler K, L\u00fcbke JHR (2016) Development of synaptic boutons in layer 4 of the barrel field of the rat somatosensory cortex: a quantitative analysis. Cereb Cortex 26:838\u2013854","journal-title":"Cereb Cortex"},{"key":"900_CR22","first-page":"1","volume":"4","author":"\u00d8 Hammer","year":"2001","unstructured":"Hammer \u00d8, Harper AT, Ryan PD (2001) Past: paleontological statistics software package for education and data analysis. Palaeontol Electron 4:1\u20139","journal-title":"Palaeontol Electron"},{"key":"900_CR23","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1093\/cercor\/bhn141","volume":"19","author":"M Helmstaedter","year":"2009","unstructured":"Helmstaedter M, Sakmann B, Feldmeyer D (2009) Neuronal correlates of local, lateral, and translaminar inhibition with reference to cortical columns. Cereb Cortex 19:926\u2013937","journal-title":"Cereb Cortex"},{"key":"900_CR24","doi-asserted-by":"publisher","first-page":"2175","DOI":"10.1002\/cne.24196","volume":"525","author":"A Hsu","year":"2017","unstructured":"Hsu A, Luebke JI, Medalla M (2017) Comparative ultrastructural features of excitatory synapses in the visual and frontal cortices of the adult mouse and monkey. J Comp Neurol 525:2175\u20132191","journal-title":"J Comp Neurol"},{"key":"900_CR25","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1113\/jphysiol.1963.sp007079","volume":"165","author":"DH Hubel","year":"1963","unstructured":"Hubel DH, Wiesel TN (1963) Shape and arrangement of columns in cat\u2019s striate cortex. J Physiol 165:559\u2013568","journal-title":"J Physiol"},{"key":"900_CR26","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/221747a0","volume":"221","author":"DH Hubel","year":"1969","unstructured":"Hubel DH, Wiesel TN (1969) Anatomical demonstration of columns in the monkey striate cortex. Nature 221:747\u2013750","journal-title":"Nature"},{"key":"900_CR27","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0400-20.2021","author":"B Imbrosci","year":"2022","unstructured":"Imbrosci B, Schmitz D, Orlando M (2022) Automated detection and localization of synaptic vesicles in electron microscopy images. eNeuro. https:\/\/doi.org\/10.1523\/ENEURO.0400-20.2021","journal-title":"eNeuro"},{"key":"900_CR28","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1038\/nprot.2013.078","volume":"8","author":"KR Kay","year":"2013","unstructured":"Kay KR, Smith C, Wright AK, Serrano-Pozo A, Pooler AM, Koffie R, Bastin ME, Bak TH, Abrahams S, Kopeikina KJ, McGuone D, Frosch MP, Gillingwater TH, Hyman BT, Spires-Jones TL (2013) Studying synapses in human brain with array tomography and electron microscopy. Nat Protoc 8:1366\u20131380","journal-title":"Nat Protoc"},{"key":"900_CR29","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1002\/cne.21007","volume":"497","author":"B Kirkpatrick","year":"2006","unstructured":"Kirkpatrick B, Xu L, Cascella N, Ozeki Y, Sawa A, Roberts RC (2006) DISC1 immunoreactivity at the light and ultrastructural level in the human neocortex. J Comp Neurol 497:436\u2013450","journal-title":"J Comp Neurol"},{"key":"900_CR30","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.brainresrev.2008.01.002","volume":"58","author":"G Knott","year":"2008","unstructured":"Knott G, Holtmaat A (2008) Dendritic spine plasticity\u2013current understanding from in vivo studies. Brain Res Rev 58:282\u2013289","journal-title":"Brain Res Rev"},{"key":"900_CR31","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/2051-5960-2-42","volume":"2","author":"XB Liu","year":"2014","unstructured":"Liu XB, Schumann CM (2014) Optimization of electron microscopy for human brains with long-term fixation and fixed-frozen sections. Acta Neuropathol Commun 2:42","journal-title":"Acta Neuropathol Commun"},{"key":"900_CR32","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.conb.2018.06.013","volume":"54","author":"HD Mansvelder","year":"2019","unstructured":"Mansvelder HD, Verhoog MB, Goriounova NA (2019) Synaptic plasticity in human cortical circuits: cellular mechanisms of learning and memory in the human brain? Curr Opin Neurobiol 54:186\u2013193. https:\/\/doi.org\/10.1016\/j.conb.2018.06.013","journal-title":"Curr Opin Neurobiol"},{"key":"900_CR33","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.neulet.2004.12.019","volume":"378","author":"DF Marrone","year":"2005","unstructured":"Marrone DF, LeBoutillier JC, Petit TL (2005) Ultrastructural correlates of vesicular docking in the rat dentate gyrus. Neurosci Lett 378:92\u201397","journal-title":"Neurosci Lett"},{"key":"900_CR34","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1016\/j.nic.2022.04.002","volume":"32","author":"EH Middlebrooks","year":"2022","unstructured":"Middlebrooks EH, Grewal SS (2022) Brain connectomics. Neuroimaging Clin N Am 32:543\u2013552","journal-title":"Neuroimaging Clin N Am"},{"key":"900_CR35","doi-asserted-by":"publisher","first-page":"4839","DOI":"10.1093\/cercor\/bhv188","volume":"25","author":"H Mohan","year":"2015","unstructured":"Mohan H, Verhoog MB, Doreswamy KK, Eyal G, Aardse R, Lodder BN, Goriounova NA, Asamoah B et al (2015) Dendritic and axonal architecture of individual pyramidal neurons across layers of adult human neocortex. Cereb Cortex 25:4839\u20134853","journal-title":"Cereb Cortex"},{"key":"900_CR36","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.18167","author":"G Molnar","year":"2016","unstructured":"Molnar G, Rozsa M, Baka J, Holderith N, Barzo P, Nusser Z, Tamas G (2016) Human pyramidal to interneuron synapses are mediated by multi-vesicular release and multiple docked vesicles. Elife. https:\/\/doi.org\/10.7554\/eLife.18167","journal-title":"Elife"},{"key":"900_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2022.119214","volume":"256","author":"M Murgas","year":"2022","unstructured":"Murgas M, Michenthaler P, Reed MB, Gryglewski G, Lanzenberger R (2022) Correlation of receptor density and mRNA expression patterns in the human cerebral cortex. Neuroimage 256:119214","journal-title":"Neuroimage"},{"key":"900_CR38","doi-asserted-by":"publisher","DOI":"10.1101\/2024.12.02.626387","author":"S Muth","year":"2024","unstructured":"Muth S, Moschref F, Freckmann L, Mutschall S, Hojas-Garcia-Plaza I, Bahr JN, Petrovic A, Thanh Thao D, Schwarze V, Archit A, Weyand K, Michanski S, Maus L, Imig C, Brose N, Wichmann C et al (2024) SynapseNet: deep learning for automatic synapse reconstruction. Biorxiv Preprint. https:\/\/doi.org\/10.1101\/2024.12.02.626387","journal-title":"Biorxiv Preprint"},{"key":"900_CR39","doi-asserted-by":"publisher","first-page":"23721","DOI":"10.1038\/srep23721","volume":"6","author":"HB Nguyen","year":"2016","unstructured":"Nguyen HB et al (2016) Conductive resins improve charging and resolution of acquired images in electron microscopic volume imaging. Sci Rep 6:23721","journal-title":"Sci Rep"},{"key":"900_CR40","doi-asserted-by":"publisher","first-page":"4101","DOI":"10.1038\/s41467-018-06628-w","volume":"9","author":"J Obermayer","year":"2018","unstructured":"Obermayer J, Heistek TS, Kerkhofs A, Goriounova NA, Kroon T, Baayen JC, Idem S, Testa-Silva G, Couey JJ, Mansvelder D (2018) Lateral inhibition by martinotti interneurons is facilitated by cholinergic inputs in human and mouse neocortex. Nat Commun 9:4101. https:\/\/doi.org\/10.1038\/s41467-018-06628-w","journal-title":"Nat Commun"},{"key":"900_CR41","doi-asserted-by":"publisher","first-page":"3209","DOI":"10.1093\/cercor\/bhz304","volume":"30","author":"M Prume","year":"2020","unstructured":"Prume M, Rollenhagen A, Yakoubi R, S\u00e4tzler K, L\u00fcbke JHR (2020) Quantitative three-dimensional reconstructions of excitatory synaptic boutons in the \u201cbarrel field\u201d of the adult \u201creeler\u201d mouse somatosensory neocortex: a comparative fine-scale electron microscopic analysis with the wild type mouse. Cereb Cortex 30:3209\u20133227","journal-title":"Cereb Cortex"},{"key":"900_CR42","doi-asserted-by":"publisher","first-page":"12099","DOI":"10.1073\/pnas.0807271105","volume":"105","author":"P Rakic","year":"2008","unstructured":"Rakic P (2008) Confusing cortical columns. Proc Natl Acad Sci USA 105:12099\u201312100","journal-title":"Proc Natl Acad Sci USA"},{"key":"900_CR43","doi-asserted-by":"publisher","first-page":"1247","DOI":"10.1007\/s00429-021-02437-y","volume":"227","author":"L Rapan","year":"2022","unstructured":"Rapan L, Niu M, Zhao L, Funck T, Amunts K, Zilles K, Palomero-Gallagher N (2022) Receptor architecture of macaque and human early visual areas: not equal, but comparable. Brain Struct Funct 227:1247\u20131263","journal-title":"Brain Struct Funct"},{"key":"900_CR44","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1083\/jcb.17.1.208","volume":"17","author":"ES Reynolds","year":"1963","unstructured":"Reynolds ES (1963) The use of lead citrate at high pH as an electron-opaque stain in electron microscopy. J Cell Biol 17:208\u2013212","journal-title":"J Cell Biol"},{"key":"900_CR45","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nrn1583","volume":"6","author":"SO Rizzoli","year":"2005","unstructured":"Rizzoli SO, Betz WJ (2005) Synaptic vesicle pools. Nat Rev Neurosci 6:57\u201369","journal-title":"Nat Rev Neurosci"},{"key":"900_CR46","doi-asserted-by":"publisher","DOI":"10.3389\/fnana.2018.00078","volume":"12","author":"KS Rockland","year":"2018","unstructured":"Rockland KS, DeFelipe J (2018) Editorial: why have cortical layers? What is the function of layering? Do neurons in cortex integrate information across different layers? Front Neuroanat 12:78","journal-title":"Front Neuroanat"},{"key":"900_CR47","doi-asserted-by":"publisher","first-page":"3159","DOI":"10.1093\/cercor\/bhx187","volume":"28","author":"J Rodriguez-Moreno","year":"2018","unstructured":"Rodriguez-Moreno J, Rollenhagen A, Arlandis J, Santuy A, Merchan-Perez A, DeFelipe J, Lubke JHR, Clasca F (2018) Quantitative 3D ultrastructure of thalamocortical synapses from the \u201clemniscal\u201d ventral posteromedial nucleus in mouse barrel cortex. Cereb Cortex 28:3159\u20133175","journal-title":"Cereb Cortex"},{"key":"900_CR48","doi-asserted-by":"publisher","first-page":"10434","DOI":"10.1523\/JNEUROSCI.1946-07.2007","volume":"27","author":"A Rollenhagen","year":"2007","unstructured":"Rollenhagen A, S\u00e4tzler K, Rodriguez EP, Jonas P, Frotscher M, L\u00fcbke JHR (2007) Structural determinants of transmission at large hippocampal mossy fiber synapses. J Neurosci 27:10434\u201310444","journal-title":"J Neurosci"},{"key":"900_CR49","doi-asserted-by":"publisher","first-page":"3185","DOI":"10.1007\/s00429-014-0850-5","volume":"220","author":"A Rollenhagen","year":"2015","unstructured":"Rollenhagen A, Klook K, S\u00e4tzler K, Qi G, Anst\u00f6tz M, Feldmeyer D, L\u00fcbke JHR (2015) Structural determinants underlying the high efficacy of synaptic transmission and plasticity at synaptic boutons in layer 4 of the adult rat \u201cbarrel cortex.\u201d Brain Struct Funct 220:3185\u20133209","journal-title":"Brain Struct Funct"},{"key":"900_CR50","doi-asserted-by":"publisher","DOI":"10.3389\/fnsyn.2018.00024","volume":"10","author":"A Rollenhagen","year":"2018","unstructured":"Rollenhagen A, Ohana O, S\u00e4tzler K, Hilgetag CC, Kuhl D, L\u00fcbke JHR (2018) Structural properties of synaptic transmission and temporal dynamics at excitatory layer 5B synapses in the adult rat somatosensory cortex. Front Synaptic Neurosci 10:24","journal-title":"Front Synaptic Neurosci"},{"key":"900_CR51","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21155558","author":"A Rollenhagen","year":"2020","unstructured":"Rollenhagen A, Walkenfort B, Yakoubi R, Klauke SA, Schmuhl-Giesen SF, Heinen-Weiler J, Voortmann S, Marshallsay B et al (2020) Synaptic organization of the human temporal lobe neocortex as revealed by high-resolution transmission, focused ion beam scanning, and electron microscopic tomography. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms21155558","journal-title":"Int J Mol Sci"},{"key":"900_CR52","doi-asserted-by":"publisher","first-page":"99473","DOI":"10.7554\/eLife.99473","volume":"13","author":"A Rollenhagen","year":"2025","unstructured":"Rollenhagen A, Sadeghi A, Walkenfort B, S\u00e4tzler K, Hilgetag CC, L\u00fcbke JHR (2025) Ultrastructural sublaminar-specific diversity of excitatory synaptic boutons in layer 1 of the adult human temporal lobe neocortex. Elife 13:99473","journal-title":"Elife"},{"key":"900_CR53","doi-asserted-by":"publisher","first-page":"10567","DOI":"10.1523\/JNEUROSCI.22-24-10567.2002","volume":"22","author":"K S\u00e4tzler","year":"2002","unstructured":"S\u00e4tzler K, S\u00f6hl LF, Bollmann JH, Borst JG, Frotscher M, Sakmann B, L\u00fcbke JHR (2002) Three-dimensional reconstruction of a calyx of Held and its postsynaptic principal neuron in the medial nucleus of the trapezoid body. J Neurosci 22:10567\u201310579","journal-title":"J Neurosci"},{"key":"900_CR54","doi-asserted-by":"publisher","first-page":"1840","DOI":"10.1093\/cercor\/bhab315","volume":"32","author":"S Schmuhl-Giesen","year":"2022","unstructured":"Schmuhl-Giesen S, Rollenhagen A, Walkenfort B, Yakoubi R, Satzler K, Miller D, von Lehe M, Hasenberg M et al (2022) Sublamina-specific dynamics and ultrastructural heterogeneity of layer 6 excitatory synaptic boutons in the adult human temporal lobe neocortex. Cereb Cortex 32:1840\u20131865","journal-title":"Cereb Cortex"},{"key":"900_CR55","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.37349","author":"SC Seeman","year":"2018","unstructured":"Seeman SC, Campagnola L, Davoudian PA, Hoggarth A, Hage TA, Bosma-Moody A, Baker CA, Lee JH, Mihalas S, Teeter C et al (2018a) Sparse recurrent excitatory connectivity in the microcircuit of the adult mouse and human cortex. Elife. https:\/\/doi.org\/10.7554\/eLife.37349","journal-title":"Elife"},{"key":"900_CR56","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.37349","author":"SC Seeman","year":"2018","unstructured":"Seeman SC, Campagnola L, Davoudian PA, Hoggarth A, Hage TA, Bosma-Moody A, Baker CA, Lee JH et al (2018b) Sparse recurrent excitatory connectivity in the microcircuit of the adult mouse and human cortex. Elife. https:\/\/doi.org\/10.7554\/eLife.37349","journal-title":"Elife"},{"key":"900_CR57","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41583-023-00718-5","volume":"24","author":"C Seguin","year":"2023","unstructured":"Seguin C, Sporns O, Zalesky A (2023a) Brain network communication: concepts, models and applications. Nat Rev Neurosci 24:557\u2013574","journal-title":"Nat Rev Neurosci"},{"issue":"1391\u20131401","key":"900_CR58","volume":"111","author":"C Seguin","year":"2023","unstructured":"Seguin C, Jedynak M, David O, Mansour S, Sporns O, Zalesky A (2023b) Communication dynamics in the human connectome shape the cortex-wide propagation of direct electrical stimulation. Neuron 111(1391\u20131401):e1395","journal-title":"Neuron"},{"key":"900_CR59","doi-asserted-by":"publisher","DOI":"10.1126\/science.adk4858","volume":"384","author":"A Shapson-Coe","year":"2024","unstructured":"Shapson-Coe A, Januszewski M, Berger DR, Pope A, Wu Y, Blakely T, Schalek RL, Li PH et al (2024) A petavoxel fragment of human cerebral cortex reconstructed at nanoscale resolution. Science 384:eadk4858","journal-title":"Science"},{"key":"900_CR60","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1111\/nan.12458","volume":"44","author":"XY Tai","year":"2018","unstructured":"Tai XY, Bernhardt B, Thom M, Thompson P, Baxendale S, Koepp M, Bernasconi N (2018) Neurodegenerative processes in temporal lobe epilepsy with hippocampal sclerosis: clinical, pathological and neuroimaging evidence. Neuropathol Appl Neurobiol 44:70\u201390","journal-title":"Neuropathol Appl Neurobiol"},{"key":"900_CR61","first-page":"12","volume":"2","author":"G Testa-Silva","year":"2010","unstructured":"Testa-Silva G, Verhoog MB, Goriounova NA, Loebel A, Hjorth J, Baayen JC, de Kock CP, Mansvelder HD (2010) Human synapses show a wide temporal window for spike-timing-dependent plasticity. Front Synaptic Neurosci 2:12","journal-title":"Front Synaptic Neurosci"},{"key":"900_CR62","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002007","volume":"12","author":"G Testa-Silva","year":"2014","unstructured":"Testa-Silva G, Verhoog MB, Linaro D, de Kock CP, Baayen JC, Meredith RM, De Zeeuw CI, Giugliano M et al (2014) High bandwidth synaptic communication and frequency tracking in human neocortex. PLoS Biol 12:e1002007","journal-title":"PLoS Biol"},{"key":"900_CR63","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-4019-7","volume-title":"New aspects in analyzing the synaptic organization of the brain, neuromethods","author":"M Turegano-Lopez","year":"2024","unstructured":"Turegano-Lopez M, Rodr\u00edguez JR, DeFelipe J, Merch\u00e1n-P\u00e9rez A (2024) Cell labeling and FIB-SEM imaging. In: L\u00fcbke JHR, Rollenhagen A (eds) New aspects in analyzing the synaptic organization of the brain, neuromethods. Springer US, NY. https:\/\/doi.org\/10.1007\/978-1-0716-4019-7"},{"key":"900_CR64","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.47434","author":"JH Vaden","year":"2019","unstructured":"Vaden JH, Banumurthy G, Gusarevich ES, Overstreet-Wadiche L, Wadiche JI (2019) The readily-releasable pool dynamically regulates multivesicular release. Elife. https:\/\/doi.org\/10.7554\/eLife.47434","journal-title":"Elife"},{"key":"900_CR65","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1016\/j.neuron.2005.06.018","volume":"47","author":"P Verstreken","year":"2005","unstructured":"Verstreken P, Ly CV, Venken KJ, Koh TW, Zhou Y, Bellen HJ (2005) Synaptic mitochondria are critical for mobilization of reserve pool vesicles at Drosophila neuromuscular junctions. Neuron 47:365\u2013378","journal-title":"Neuron"},{"key":"900_CR66","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/978-1-59745-178-9_26","volume":"440","author":"P Verstreken","year":"2008","unstructured":"Verstreken P, Ohyama T, Bellen HJ (2008) FM 1\u201343 labeling of synaptic vesicle pools at the Drosophila neuromuscular junction. Methods Mol Biol 440:349\u2013369","journal-title":"Methods Mol Biol"},{"key":"900_CR67","volume-title":"Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen","author":"C von Economo","year":"1925","unstructured":"von Economo C, Koskinas GN (1925) Die Cytoarchitektonik der Hirnrinde des erwachsenen Menschen. Verlag J. Springer, Wien und Berlin"},{"key":"900_CR68","doi-asserted-by":"publisher","first-page":"2182","DOI":"10.1523\/JNEUROSCI.23-06-02182.2003","volume":"23","author":"MA Xu-Friedman","year":"2003","unstructured":"Xu-Friedman MA, Regehr WG (2003) Ultrastructural contributions to desensitization at cerebellar mossy fiber to granule cell synapses. J Neurosci 23:2182\u20132192","journal-title":"J Neurosci"},{"key":"900_CR69","doi-asserted-by":"publisher","first-page":"6666","DOI":"10.1523\/JNEUROSCI.21-17-06666.2001","volume":"21","author":"MA Xu-Friedman","year":"2001","unstructured":"Xu-Friedman MA, Harris KM, Regehr WG (2001) Three-dimensional comparison of ultrastructural characteristics at depressing and facilitating synapses onto cerebellar Purkinje cells. J Neurosci 21:6666\u20136672","journal-title":"J Neurosci"},{"key":"900_CR70","doi-asserted-by":"publisher","first-page":"e48373","DOI":"10.7554\/eLife.48373","volume":"8","author":"R Yakoubi","year":"2019","unstructured":"Yakoubi R, Rollenhagen A, von Lehe M, Miller D, Walkenfort B, Hasenberg M, S\u00e4tzler K, L\u00fcbke JHR (2019a) Ultrastructural heterogeneity of layer 4 excitatory synaptic boutons in the adult human temporal lobe neocortex. Elife 8:e48373","journal-title":"Elife"},{"key":"900_CR71","doi-asserted-by":"publisher","first-page":"2797","DOI":"10.1093\/cercor\/bhy146","volume":"29","author":"R Yakoubi","year":"2019","unstructured":"Yakoubi R, Rollenhagen A, von Lehe M, Shao Y, S\u00e4tzler K, L\u00fcbke JHR (2019b) Quantitative three-dimensional reconstructions of excitatory synaptic boutons in layer 5 of the adult human temporal lobe neocortex: a fine-scale electron microscopic analysis. Cereb Cortex 29:2797\u20132814","journal-title":"Cereb Cortex"}],"container-title":["Anatomical Science International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12565-025-00900-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12565-025-00900-y\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12565-025-00900-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T10:03:09Z","timestamp":1760090589000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12565-025-00900-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":71,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["900"],"URL":"https:\/\/doi.org\/10.1007\/s12565-025-00900-y","relation":{},"ISSN":["1447-6959","1447-073X"],"issn-type":[{"value":"1447-6959","type":"print"},{"value":"1447-073X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"11 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that they have no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}