{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:28:59Z","timestamp":1790162939050,"version":"4.1.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T00:00:00Z","timestamp":1737504000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Psychiatry"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Perineuronal nets (PNNs) are a condensed form of extracellular matrix primarily found around parvalbumin-expressing (PV+) interneurons. The postnatal maturation of PV+ neurons is accompanied with the formation of PNNs and reduced plasticity. Alterations in PNN and PV+ neuron function have been described for mental disorders such as schizophrenia and autism. The formation of PNNs is highly dependent on aggrecan, a proteoglycan encoded by the ACAN gene, but it remains unknown if it is produced by the PV+ neurons themselves. Thus, we established a knockout (KO) mouse model (ACANflx\/PVcre) and an adeno-associated virus to specifically eliminate aggrecan production from PV+ neurons, in the germline or adult animals, respectively. The germline KO (ACANflx\/PVcre) eliminated the expression of PNNs labeled by\n                    <jats:italic>Wisteria floribunda<\/jats:italic>\n                    agglutinin (WFA), the most commonly used PNN marker. Surprisingly, electrophysiological properties of PV+ interneurons and ocular dominance plasticity of adult ACANflx\/PVcre mice were similar to controls. In contrast, AAV-mediated ACAN knockout in adult mice increased ocular dominance plasticity. Moreover, in vivo Chondroitinase ABC treatment of KO mice resulted in reduced firing rate of PV+ cells and increased frequency of spontaneous excitatory postsynaptic currents (sEPSC), a phenotype associated with chABC treatment of WT animals. These findings suggest that compensatory mechanisms may be activated during development in response to the germline loss of aggrecan. Indeed, qPCR of bulk tissue indicates that other PNN components, including neurocan and tenascin-R, are expressed at higher levels in the KO animals. Finally, behavioral testing revealed that ACANflx\/PVcre mice had similar long-term memory as controls in the Morris water maze. However, they employed bolder search strategies during spatial learning and showed lower level of anxiety-related behavior in an open field and zero maze.\n                  <\/jats:p>","DOI":"10.1038\/s41380-025-02894-5","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T19:44:02Z","timestamp":1737488642000},"page":"2907-2921","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Differential impacts of germline and adult aggrecan knockout in PV+ neurons on perineuronal nets and PV+ neuronal function"],"prefix":"10.1038","volume":"30","author":[{"given":"Sverre","family":"Gr\u00f8dem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise Holter","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malin Benum","family":"R\u00f8e","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guro Helen","family":"Vatne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingeborg","family":"Nymoen Nystuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessio","family":"Buccino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarjei","family":"Otterstad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0928-3487","authenticated-orcid":false,"given":"Torkel","family":"Hafting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianne","family":"Fyhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3145-1659","authenticated-orcid":false,"given":"Kristian Kinden","family":"Lensj\u00f8","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"2894_CR1","doi-asserted-by":"crossref","first-page":"3960","DOI":"10.1111\/ejn.15009","volume":"53","author":"H Pantazopoulos","year":"2021","unstructured":"Pantazopoulos H, Katsel P, Haroutunian V, Chelini G, Klengel T, Berretta S. Molecular signature of extracellular matrix pathology in schizophrenia. Eur J Neurosci. 2021;53:3960\u201387.","journal-title":"Eur J Neurosci"},{"key":"2894_CR2","doi-asserted-by":"crossref","first-page":"27384","DOI":"10.1074\/jbc.M111.310029","volume":"288","author":"G Dick","year":"2013","unstructured":"Dick G, Tan CL, Alves JN, Ehlert EMEE, Miller GM, Hsieh-Wilson LC, et al. Semaphorin 3A binds to the perineuronal nets via chondroitin sulfate type E motifs in rodent brains. J Biol Chem. 2013;288:27384\u201395.","journal-title":"J Biol Chem"},{"key":"2894_CR3","doi-asserted-by":"crossref","first-page":"9429","DOI":"10.1523\/JNEUROSCI.0394-12.2012","volume":"32","author":"M Beurdeley","year":"2012","unstructured":"Beurdeley M, Spatazza J, Lee HHC, Sugiyama S, Bernard C, Di Nardo AA, et al. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J Neurosci. 2012;32:9429\u201337.","journal-title":"J Neurosci"},{"key":"2894_CR4","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1016\/j.cell.2008.05.054","volume":"134","author":"S Sugiyama","year":"2008","unstructured":"Sugiyama S, Di Nardo AA, Aizawa S, Matsuo I, Volovitch M, Prochiantz A, et al. Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity. Cell. 2008;134:508\u201320.","journal-title":"Cell"},{"key":"2894_CR5","doi-asserted-by":"crossref","first-page":"10102","DOI":"10.1523\/JNEUROSCI.1122-18.2018","volume":"38","author":"D Rowlands","year":"2018","unstructured":"Rowlands D, Lensj\u00f8 KK, Dinh T, Yang S, Andrews MR, Hafting T, et al. Aggrecan directs extracellular matrix-mediated neuronal plasticity. J Neurosci. 2018;38:10102\u201313.","journal-title":"J Neurosci"},{"key":"2894_CR6","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1097\/00001756-199210000-00012","volume":"3","author":"W H\u00e4rtig","year":"1992","unstructured":"H\u00e4rtig W, Brauer K, Br\u00fcckner G. Wisteria floribunda agglutinin-labelled nets surround parvalbumin-containing neurons. Neuroreport. 1992;3:869\u201372.","journal-title":"Neuroreport"},{"key":"2894_CR7","doi-asserted-by":"crossref","first-page":"ENEURO.0379-16.","DOI":"10.1523\/ENEURO.0379-16.2017","volume":"4","author":"KK Lensj\u00f8","year":"2017","unstructured":"Lensj\u00f8 KK, Christensen AC, Tenn\u00f8e S, Fyhn M, Hafting T. Differential expression and cell-type specificity of perineuronal nets in hippocampus, medial entorhinal cortex, and visual cortex examined in the rat and mouse. Eneuro. 2017;4:ENEURO.0379-16.2017.","journal-title":"Eneuro"},{"key":"2894_CR8","doi-asserted-by":"crossref","first-page":"112788","DOI":"10.1016\/j.celrep.2023.112788","volume":"42","author":"L Lupori","year":"2023","unstructured":"Lupori L, Totaro V, Cornuti S, Ciampi L, Carrara F, Grilli E, et al. A comprehensive atlas of perineuronal net distribution and colocalization with parvalbumin in the adult mouse brain. Cell Rep. 2023;42:112788.","journal-title":"Cell Rep"},{"key":"2894_CR9","volume":"345","author":"H Hu","year":"2014","unstructured":"Hu H, Gan J, Jonas P. Fast-spiking, parvalbumin+ GABAergic interneurons: From cellular design to microcircuit function. Science. 2014;345:1255263.","journal-title":"Science"},{"key":"2894_CR10","doi-asserted-by":"crossref","first-page":"37","DOI":"10.3389\/fncir.2018.00037","volume":"12","author":"BR Ferguson","year":"2018","unstructured":"Ferguson BR, Gao W-J. PV Interneurons: critical regulators of E\/I balance for prefrontal cortex-dependent behavior and psychiatric disorders. Front Neural Circuits. 2018;12:37.","journal-title":"Front Neural Circuits"},{"key":"2894_CR11","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.neuron.2011.09.027","volume":"72","author":"JS Isaacson","year":"2011","unstructured":"Isaacson JS, Scanziani M. How inhibition shapes cortical activity. Neuron. 2011;72:231\u201343.","journal-title":"Neuron"},{"key":"2894_CR12","doi-asserted-by":"crossref","DOI":"10.1038\/srep46024","volume":"7","author":"S Morikawa","year":"2017","unstructured":"Morikawa S, Ikegaya Y, Narita M, Tamura H. Activation of perineuronal net-expressing excitatory neurons during associative memory encoding and retrieval. Sci Rep. 2017;7:46024.","journal-title":"Sci Rep"},{"key":"2894_CR13","doi-asserted-by":"crossref","first-page":"120","DOI":"10.3389\/fphar.2012.00120","volume":"3","author":"S Wiese","year":"2012","unstructured":"Wiese S, Karus M, Faissner A. Astrocytes as a source for extracellular matrix molecules and cytokines. Front Pharmacol. 2012;3:120.","journal-title":"Front Pharmacol"},{"key":"2894_CR14","doi-asserted-by":"crossref","first-page":"1022754","DOI":"10.3389\/fncel.2022.1022754","volume":"16","author":"BP Tewari","year":"2022","unstructured":"Tewari BP, Chaunsali L, Prim CE, Sontheimer H. A glial perspective on the extracellular matrix and perineuronal net remodeling in the central nervous system. Front Cell Neurosci. 2022;16:1022754.","journal-title":"Front Cell Neurosci"},{"key":"2894_CR15","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.neuroscience.2012.05.055","volume":"218","author":"KA Giamanco","year":"2012","unstructured":"Giamanco KA, Matthews RT. Deconstructing the perineuronal net: cellular contributions and molecular composition of the neuronal extracellular matrix. Neuroscience. 2012;218:367\u201384.","journal-title":"Neuroscience"},{"key":"2894_CR16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-50404-9","volume":"9","author":"C Gottschling","year":"2019","unstructured":"Gottschling C, Wegrzyn D, Denecke B, Faissner A. Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses. Sci Rep. 2019;9:1\u201317.","journal-title":"Sci Rep"},{"key":"2894_CR17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.neuroscience.2005.07.031","volume":"136","author":"S Miyata","year":"2005","unstructured":"Miyata S, Nishimura Y, Hayashi N, Oohira A. Construction of perineuronal net-like structure by cortical neurons in culture. Neuroscience. 2005;136:95\u2013104.","journal-title":"Neuroscience"},{"key":"2894_CR18","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.neuron.2017.06.028","volume":"95","author":"E Favuzzi","year":"2017","unstructured":"Favuzzi E, Marques-Smith A, Deogracias R, Winterflood CM, S\u00e1nchez-Aguilera A, Mantoan L, et al. Activity-dependent gating of parvalbumin interneuron function by the perineuronal net protein brevican. Neuron. 2017;95:639\u201355.e10.","journal-title":"Neuron"},{"key":"2894_CR19","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1523\/JNEUROSCI.2504-16.2016","volume":"37","author":"KK Lensj\u00f8","year":"2017","unstructured":"Lensj\u00f8 KK, Lepper\u00f8d ME, Dick G, Hafting T, Fyhn M. Removal of perineuronal nets unlocks juvenile plasticity through network mechanisms of decreased inhibition and increased gamma activity. J Neurosci. 2017;37:1269\u201383.","journal-title":"J Neurosci"},{"key":"2894_CR20","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1038\/nm.4225","volume":"22","author":"O Mar\u00edn","year":"2016","unstructured":"Mar\u00edn O. Developmental timing and critical windows for the treatment of psychiatric disorders. Nat Med. 2016;22:1229\u201338.","journal-title":"Nat Med"},{"key":"2894_CR21","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-07113-0","volume":"9","author":"BP Tewari","year":"2018","unstructured":"Tewari BP, Chaunsali L, Campbell SL, Patel DC, Goode AE, Sontheimer H. Perineuronal nets decrease membrane capacitance of peritumoral fast spiking interneurons in a model of epilepsy. Nat Commun. 2018;9:4724.","journal-title":"Nat Commun"},{"key":"2894_CR22","doi-asserted-by":"crossref","first-page":"673210","DOI":"10.3389\/fnsyn.2021.673210","volume":"13","author":"JC Wingert","year":"2021","unstructured":"Wingert JC, Sorg BA. Impact of perineuronal nets on electrophysiology of parvalbumin interneurons, principal neurons, and brain oscillations: a review. Front Synaptic Neurosci. 2021;13:673210.","journal-title":"Front Synaptic Neurosci"},{"key":"2894_CR23","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.neuroscience.2018.07.004","volume":"388","author":"P Chu","year":"2018","unstructured":"Chu P, Abraham R, Budhu K, Khan U, De Marco Garcia N, Brumberg JC. The impact of perineuronal net digestion using chondroitinase abc on the intrinsic physiology of cortical neurons. Neuroscience. 2018;388:23\u201335.","journal-title":"Neuroscience"},{"key":"2894_CR24","doi-asserted-by":"crossref","first-page":"e41520","DOI":"10.7554\/eLife.41520","volume":"7","author":"G Faini","year":"2018","unstructured":"Faini G, Aguirre A, Landi S, Lamers D, Pizzorusso T, Ratto GM, et al. Perineuronal nets control visual input via thalamic recruitment of cortical PV interneurons. Elife. 2018;7:e41520.","journal-title":"Elife"},{"key":"2894_CR25","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fncel.2018.00149","volume":"12","author":"H Hayani","year":"2018","unstructured":"Hayani H, Song I, Dityatev A. Increased excitability and reduced excitatory synaptic input into fast-spiking CA2 interneurons after enzymatic attenuation of extracellular matrix. Front Cell Neurosci. 2018;12:149.","journal-title":"Front Cell Neurosci"},{"key":"2894_CR26","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1523\/ENEURO.0112-16.2016","volume":"3","author":"TS Balmer","year":"2016","unstructured":"Balmer TS. Perineuronal nets enhance the excitability of fast-spiking neurons. ENeuro. 2016;3:745\u201351.","journal-title":"ENeuro"},{"key":"2894_CR27","doi-asserted-by":"crossref","first-page":"136763","DOI":"10.1016\/j.neulet.2022.136763","volume":"785","author":"L Liu","year":"2022","unstructured":"Liu L, Zhang Y, Ju J. Removal of perineuronal nets leads to altered neuronal excitability and synaptic transmission in the visual cortex with distinct time courses. Neurosci Lett. 2022;785:136763.","journal-title":"Neurosci Lett"},{"key":"2894_CR28","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1002\/hipo.23503","volume":"33","author":"L Liu","year":"2023","unstructured":"Liu L, Zhang Y, Men S, Li X, Hou ST, Ju J. Elimination of perineuronal nets in CA1 disrupts GABA release and long-term contextual fear memory retention. Hippocampus. 2023;33:862\u201371.","journal-title":"Hippocampus"},{"key":"2894_CR29","doi-asserted-by":"crossref","first-page":"17789","DOI":"10.1074\/jbc.M600544200","volume":"281","author":"SS Deepa","year":"2006","unstructured":"Deepa SS, Carulli D, Galtrey C, Rhodes K, Fukuda J, Mikami T, et al. Composition of perineuronal net extracellular matrix in rat brain: a different disaccharide composition for the net-associated proteoglycans. J Biol Chem. 2006;281:17789\u2013800.","journal-title":"J Biol Chem"},{"key":"2894_CR30","doi-asserted-by":"crossref","first-page":"0878","DOI":"10.1371\/journal.pbio.0030159","volume":"3","author":"S Hippenmeyer","year":"2005","unstructured":"Hippenmeyer S, Vrieseling E, Sigrist M, Portmann T, Laengle C, Ladle DR, et al. A developmental switch in the response of DRG neurons to ETS transcription factor signaling. PLoS Biol. 2005;3:0878\u201390.","journal-title":"PLoS Biol"},{"key":"2894_CR31","doi-asserted-by":"crossref","first-page":"5779","DOI":"10.1523\/JNEUROSCI.0434-21.2021","volume":"41","author":"G Devienne","year":"2021","unstructured":"Devienne G, Picaud S, Cohen I, Piquet J, Tricoire L, Testa D, et al. Regulation of perineuronal nets in the adult cortex by the activity of the cortical network. J Neurosci. 2021;41:5779.","journal-title":"J Neurosci"},{"key":"2894_CR32","doi-asserted-by":"crossref","first-page":"6312","DOI":"10.1523\/JNEUROSCI.0245-16.2016","volume":"36","author":"KE Carstens","year":"2016","unstructured":"Carstens KE, Phillips ML, Pozzo-Miller L, Weinberg RJ, Dudek SM. Perineuronal nets suppress plasticity of excitatory synapses on CA2 pyramidal neurons. J Neurosci. 2016;36:6312\u201320.","journal-title":"J Neurosci"},{"key":"2894_CR33","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1038\/s41593-020-0692-9","volume":"23","author":"D Vormstein-Schneider","year":"2020","unstructured":"Vormstein-Schneider D, Lin JD, Pelkey KA, Chittajallu R, Guo B, Arias-Garcia MA, et al. Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans. Nat Neurosci. 2020;23:1629\u201336.","journal-title":"Nat Neurosci"},{"key":"2894_CR34","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/j.neuron.2015.05.027","volume":"86","author":"B Amilhon","year":"2015","unstructured":"Amilhon B, Huh CYL, Manseau F, Ducharme G, Nichol H, Adamantidis A, et al. Parvalbumin interneurons of hippocampus tune population activity at theta frequency. Neuron. 2015;86:1277\u201389.","journal-title":"Neuron"},{"key":"2894_CR35","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1038\/nature08002","volume":"459","author":"JA Cardin","year":"2009","unstructured":"Cardin JA, Carl\u00e9n M, Meletis K, Knoblich U, Zhang F, Deisseroth K, et al. Driving fast-spiking cells induces gamma rhythm and controls sensory responses. Nature. 2009;459:663\u20137.","journal-title":"Nature"},{"key":"2894_CR36","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1038\/nature07991","volume":"459","author":"VS Sohal","year":"2009","unstructured":"Sohal VS, Zhang F, Yizhar O, Deisseroth K. Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature. 2009;459:698\u2013702.","journal-title":"Nature"},{"key":"2894_CR37","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1016\/j.neuron.2004.12.003","volume":"44","author":"MY Frenkel","year":"2004","unstructured":"Frenkel MY, Bear MF. How monocular deprivation shifts ocular dominance in visual cortex of young mice. Neuron. 2004;44:917\u201323.","journal-title":"Neuron"},{"key":"2894_CR38","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1523\/JNEUROSCI.16-10-03274.1996","volume":"16","author":"JA Gordon","year":"1996","unstructured":"Gordon JA, Stryker MP. Experience-dependent plasticity of binocular responses in the primary visual cortex of the mouse. J Neurosci. 1996;16:3274\u201386.","journal-title":"J Neurosci"},{"key":"2894_CR39","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1152\/jn.1963.26.6.1003","volume":"26","author":"TN Wiesel","year":"1963","unstructured":"Wiesel TN, Hubel DH. Single-cell responses in striate cortex of kittens deprived of vision in one eye. J Neurophysiol. 1963;26:1003\u201317.","journal-title":"J Neurophysiol"},{"key":"2894_CR40","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1126\/science.1072699","volume":"298","author":"T Pizzorusso","year":"2002","unstructured":"Pizzorusso T, Medini P, Berardi N, Chierzi S, Fawcett JW, Maffei L. Reactivation of ocular dominance plasticity in the adult visual cortex. Science. 2002;298:1248\u201351.","journal-title":"Science"},{"key":"2894_CR41","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/0023-9690(81)90020-5","volume":"12","author":"RGM Morris","year":"1981","unstructured":"Morris RGM. Spatial localization does not require the presence of local cues. Learn Motiv. 1981;12:239\u201360.","journal-title":"Learn Motiv"},{"key":"2894_CR42","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.12688\/f1000research.20352.1","volume":"8","author":"MB Cooke","year":"2019","unstructured":"Cooke MB, O\u2019Leary TP, Harris P, Brown RE, Snyder JS. Pathfinder: open source software for analyzing spatial navigation search strategies. F1000Research. 2019;8:1521.","journal-title":"F1000Research"},{"key":"2894_CR43","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.bbi.2015.10.013","volume":"52","author":"T Illouz","year":"2016","unstructured":"Illouz T, Madar R, Louzon Y, Griffioen KJ, Okun E. Unraveling cognitive traits using the Morris water maze unbiased strategy classification (MUST-C) algorithm. Brain Behav Immun. 2016;52:132\u201344.","journal-title":"Brain Behav Immun"},{"key":"2894_CR44","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1016\/0091-3057(88)90413-3","volume":"31","author":"D Treit","year":"1988","unstructured":"Treit D, Fundytus M. Thigmotaxis as a test for anxiolytic activity in rats. Pharmacol Biochem Behav. 1988;31:959\u201362.","journal-title":"Pharmacol Biochem Behav"},{"key":"2894_CR45","doi-asserted-by":"crossref","first-page":"2800","DOI":"10.1073\/pnas.1310272111","volume":"111","author":"MFK Happel","year":"2014","unstructured":"Happel MFK, Niekisch H, Rivera LLC, Ohl FW, Deliano M, Frischknecht R, et al. Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex. Proc Natl Acad Sci USA. 2014;111:2800\u20135.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2894_CR46","doi-asserted-by":"crossref","first-page":"136","DOI":"10.3389\/fnbeh.2014.00136","volume":"8","author":"F Darcet","year":"2014","unstructured":"Darcet F, Mendez-David I, Tritschler L, Gardier AM, Guilloux JP, David DJ. Learning and memory impairments in a neuroendocrine mouse model of anxiety\/depression. Front Behav Neurosci. 2014;8:136.","journal-title":"Front Behav Neurosci"},{"key":"2894_CR47","doi-asserted-by":"crossref","first-page":"e0197003","DOI":"10.1371\/journal.pone.0197003","volume":"13","author":"A Higaki","year":"2018","unstructured":"Higaki A, Mogi M, Iwanami J, Min LJ, Bai HY, Shan BS, et al. Recognition of early stage thigmotaxis in morris water maze test with convolutional neural network. PLoS ONE. 2018;13:e0197003.","journal-title":"PLoS ONE"},{"key":"2894_CR48","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1111\/ejn.13192","volume":"43","author":"D Pritchett","year":"2016","unstructured":"Pritchett D, Taylor AM, Barkus C, Engle SJ, Brandon NJ, Sharp T, et al. Searching for cognitive enhancement in the Morris water maze: better and worse performance in D-amino acid oxidase knockout (Dao \u2212\/\u2212) mice. Eur J Neurosci. 2016;43:979\u201389.","journal-title":"Eur J Neurosci"},{"key":"2894_CR49","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s10827-023-00849-9","volume":"51","author":"K\u00d8 Hanssen","year":"2023","unstructured":"Hanssen K\u00d8, Gr\u00f8dem S, Fyhn M, Hafting T, Einevoll GT, Ness TV, et al. Responses in fast-spiking interneuron firing rates to parameter variations associated with degradation of perineuronal nets. J Comput Neurosci. 2023;51:283\u201398.","journal-title":"J Comput Neurosci"},{"key":"2894_CR50","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1523\/JNEUROSCI.16-02-00506.1996","volume":"16","author":"J Du","year":"1996","unstructured":"Du J, Zhang L, Weiser M, Rudy B, McBain CJ. Developmental expression and functional characterization of the potassium-channel subunit Kv3.1b in parvalbumin-containing interneurons of the rat hippocampus. J Neurosci. 1996;16:506\u201318.","journal-title":"J Neurosci"},{"key":"2894_CR51","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.neuron.2008.03.003","volume":"58","author":"EM Goldberg","year":"2008","unstructured":"Goldberg EM, Clark BD, Zagha E, Nahmani M, Erisir A, Rudy B. K+ channels at the axon initial segment dampen near-threshold excitability of neocortical fast-spiking GABAergic interneurons. Neuron. 2008;58:387\u2013400.","journal-title":"Neuron"},{"key":"2894_CR52","first-page":"ENEURO.0059-17.","volume":"4","author":"IEJ Aaseb\u00f8","year":"2017","unstructured":"Aaseb\u00f8 IEJ, Lepper\u00f8d ME, Stavrinou M, N\u00f8kkevangen S, Einevoll G, Hafting T, et al. Temporal processing in the visual cortex of the awake and anesthetized rat. ENeuro. 2017;4:ENEURO.0059-17.2017.","journal-title":"ENeuro"},{"key":"2894_CR53","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.neuropharm.2017.03.018","volume":"118","author":"JM Blacktop","year":"2017","unstructured":"Blacktop JM, Todd RP, Sorg BA. Role of perineuronal nets in the anterior dorsal lateral hypothalamic area in the acquisition of cocaine-induced conditioned place preference and self-administration. Neuropharmacology. 2017;118:124\u201336.","journal-title":"Neuropharmacology"},{"key":"2894_CR54","doi-asserted-by":"crossref","first-page":"6855","DOI":"10.1073\/pnas.1916163117","volume":"117","author":"D Carulli","year":"2020","unstructured":"Carulli D, Broersen R, de Winter F, Muir EM, Me\u0161kovic M, de Waal M, et al. Cerebellar plasticity and associative memories are controlled by perineuronal nets. Proc Natl Acad Sci USA. 2020;117:6855\u201365.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2894_CR55","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1523\/JNEUROSCI.3592-14.2015","volume":"35","author":"M Slaker","year":"2015","unstructured":"Slaker M, Churchill L, Todd RP, Blacktop JM, Zuloaga DG, Raber J, et al. Removal of perineuronal nets in the medial prefrontal cortex impairs the acquisition and reconsolidation of a cocaine-induced conditioned place preference memory. J Neurosci. 2015;35:4190\u2013202.","journal-title":"J Neurosci"},{"key":"2894_CR56","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1073\/pnas.1713530115","volume":"115","author":"EH Thompson","year":"2018","unstructured":"Thompson EH, Lensj\u00f8 KK, Wigestrand MB, Malthe-S\u00f8renssen A, Hafting T, Fyhn M. Removal of perineuronal nets disrupts recall of a remote fear memory. Proc Natl Acad Sci USA. 2018;115:607\u201312.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2894_CR57","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s12035-023-03596-1","volume":"61","author":"X Li","year":"2024","unstructured":"Li X, Ren D, Luo B, Liu Z, Li N, Zhou T, et al. Perineuronal nets alterations contribute to stress-induced anxiety-like behavior. Mol Neurobiol. 2024;61:411\u201322.","journal-title":"Mol Neurobiol"},{"key":"2894_CR58","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1037\/bne0000203","volume":"131","author":"KD Baker","year":"2017","unstructured":"Baker KD, Gray AR, Richardson R. The development of perineuronal nets around parvalbumin GABAergic neurons in the medial prefrontal cortex and basolateral amygdala of rats. Behav Neurosci. 2017;131:289\u2013303.","journal-title":"Behav Neurosci"},{"key":"2894_CR59","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1007\/s00429-013-0508-8","volume":"219","author":"A Caballero","year":"2014","unstructured":"Caballero A, Flores-Barrera E, Cass DK, Tseng KY. Differential regulation of parvalbumin and calretinin interneurons in the prefrontal cortex during adolescence. Brain Struct Funct. 2014;219:395\u2013406.","journal-title":"Brain Struct Funct"},{"key":"2894_CR60","doi-asserted-by":"crossref","first-page":"7520","DOI":"10.1523\/JNEUROSCI.0623-08.2008","volume":"28","author":"CM Niell","year":"2008","unstructured":"Niell CM, Stryker MP. Highly selective receptive fields in mouse visual cortex. J Neurosci. 2008;28:7520\u201336.","journal-title":"J Neurosci"},{"key":"2894_CR61","doi-asserted-by":"crossref","first-page":"045003","DOI":"10.1088\/1741-2552\/aa5eea","volume":"14","author":"JH Siegle","year":"2017","unstructured":"Siegle JH, L\u00f3pez AC, Patel YA, Abramov K, Ohayon S, Voigts J. Open Ephys: an open-source, plugin-based platform for multichannel electrophysiology. J Neural Eng. 2017;14:045003.","journal-title":"J Neural Eng"},{"key":"2894_CR62","doi-asserted-by":"crossref","first-page":"30","DOI":"10.3389\/fninf.2020.00030","volume":"14","author":"ME Lepper\u00f8d","year":"2020","unstructured":"Lepper\u00f8d ME, Dragly S-A, Buccino AP, Mobarhan MH, Malthe-S\u00f8renssen A, Hafting T, et al. Experimental pipeline (Expipe): a lightweight data management platform to simplify the steps from experiment to data analysis. Front Neuroinform. 2020;14:30.","journal-title":"Front Neuroinform"},{"key":"2894_CR63","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3389\/fninf.2018.00016","volume":"12","author":"S-A Dragly","year":"2018","unstructured":"Dragly S-A, Hobbi Mobarhan M, Lepper\u00f8d ME, Tenn\u00f8e S, Fyhn M, Hafting T, et al. Experimental Directory Structure (Exdir): an alternative to HDF5 without introducing a new file format. Front Neuroinform. 2018;12:16.","journal-title":"Front Neuroinform"},{"key":"2894_CR64","doi-asserted-by":"crossref","unstructured":"Lee HK, Choi Y-S. Application of continuous wavelet transform and convolutional neural network in decoding motor imagery brain-computer interface. Entropy. 2019;21:1199.","DOI":"10.3390\/e21121199"},{"key":"2894_CR65","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.jneumeth.2006.11.017","volume":"162","author":"JW Peirce","year":"2007","unstructured":"Peirce JW. PsychoPy-Psychophysics software in Python. J Neurosci Methods. 2007;162:8\u201313.","journal-title":"J Neurosci Methods"},{"key":"2894_CR66","doi-asserted-by":"publisher","unstructured":"Ting JT, Lee BR, Chong P, Soler-Llavina G, Cobbs C, Koch C, et al. Preparation of acute brain slices using an optimized N-Methyl-D-glucamine protective recovery method. J Vis Exp. 2018. https:\/\/doi.org\/10.3791\/53825.","DOI":"10.3791\/53825"},{"key":"2894_CR67","doi-asserted-by":"crossref","first-page":"4301","DOI":"10.1523\/JNEUROSCI.3488-16.2017","volume":"37","author":"T Tsintsadze","year":"2017","unstructured":"Tsintsadze T, Williams CL, Weingarten DJ, von Gersdorff H, Smith SM. Distinct actions of voltage-activated Ca2+ channel block on spontaneous release at excitatory and inhibitory central synapses. J Neurosci. 2017;37:4301\u201310.","journal-title":"J Neurosci"},{"key":"2894_CR68","unstructured":"Harden. pyabf \u00b7 PyPI. 2022. https:\/\/pypi.org\/project\/pyabf\/. Accessed 20 Mar 2024."},{"key":"2894_CR69","unstructured":"Van Geit W, Mike G, croessert, joffreygonin, Luis, jdcourcol, et al. BlueBrain\/eFEL: Pure python features. 2018."},{"key":"2894_CR70","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1152\/jn.00160.2009","volume":"102","author":"J Golowasch","year":"2009","unstructured":"Golowasch J, Thomas G, Taylor AL, Patel A, Pineda A, Khalil C, et al. Membrane capacitance measurements revisited: dependence of capacitance value on measurement method in nonisopotential neurons. J Neurophysiol. 2009;102:2161\u201375.","journal-title":"J Neurophysiol"},{"key":"2894_CR71","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/s41592-020-01018-x","volume":"18","author":"C Stringer","year":"2021","unstructured":"Stringer C, Wang T, Michaelos M, Pachitariu M. Cellpose: a generalist algorithm for cellular segmentation. Nat Methods. 2021;18:100\u20136.","journal-title":"Nat Methods"}],"container-title":["Molecular Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41380-025-02894-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-025-02894-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41380-025-02894-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T14:02:22Z","timestamp":1750687342000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41380-025-02894-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,22]]},"references-count":71,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7]]}},"alternative-id":["2894"],"URL":"https:\/\/doi.org\/10.1038\/s41380-025-02894-5","relation":{},"ISSN":["1359-4184","1476-5578"],"issn-type":[{"value":"1359-4184","type":"print"},{"value":"1476-5578","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,22]]},"assertion":[{"value":"22 March 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 December 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 January 2025","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2025","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}