article published yes Alessandro Venturino author 41CB84B2-F248-11E8-B48F-1D18A9856A870000-0003-2356-9403 Rouven Schulz author 4C5E7B96-F248-11E8-B48F-1D18A9856A870000-0001-5297-733X Héctor De Jesús-Cortés author Margaret E Maes author 3838F452-F248-11E8-B48F-1D18A9856A870000-0001-9642-1085 Balint Nagy author 93C65ECC-A6F2-11E9-8DF9-9712E6697425 Francis Reilly-Andújar author Gloria Colombo author 3483CF6C-F248-11E8-B48F-1D18A9856A870000-0001-9434-8902 Ryan J Cubero author 850B2E12-9CD4-11E9-837F-E719E66974250000-0003-0002-1867 Florianne E Schoot Uiterkamp author 3526230C-F248-11E8-B48F-1D18A9856A87 Mark F. Bear author Sandra Siegert author 36ACD32E-F248-11E8-B48F-1D18A9856A870000-0001-8635-0877 SaSi department International IST Doctoral Program project ISTplus - Postdoctoral Fellowships project Microglia action towards neuronal circuit formation and function in health and disease project Perineuronal nets (PNNs), components of the extracellular matrix, preferentially coat parvalbumin-positive interneurons and constrain critical-period plasticity in the adult cerebral cortex. Current strategies to remove PNN are long-lasting, invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic ketamine as a method with minimal behavioral effect. We find that this paradigm strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like plasticity. Microglia are critically involved in PNN loss because they engage with parvalbumin-positive neurons in their defined cortical layer. We identify external 60-Hz light-flickering entrainment to recapitulate microglia-mediated PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques, does not induce PNN loss, suggesting microglia might functionally tune to distinct brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative form of PNN intervention in the healthy adult brain. https://research-explorer.ista.ac.at/download/9642/9693/2021_CellReports_Venturino.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ Elsevier2021 eng 2211-1247 34233180 00067018850000410.1016/j.celrep.2021.109313 361 https://ist.ac.at/en/news/the-twinkle-and-the-brain/ A. Venturino <i>et al.</i>, “Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain,” <i>Cell Reports</i>, vol. 36, no. 1. Elsevier, 2021. Venturino A, Schulz R, De Jesús-Cortés H, Maes ME, Nagy B, Reilly-Andújar F, Colombo G, Cubero RJ, Miteva FE, Bear MF, Siegert S. 2021. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. Cell Reports. 36(1), 109313. Venturino, Alessandro, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>, vol. 36, no. 1, 109313, Elsevier, 2021, doi:<a href="https://doi.org/10.1016/j.celrep.2021.109313">10.1016/j.celrep.2021.109313</a>. Venturino A, Schulz R, De Jesús-Cortés H, et al. Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. 2021;36(1). doi:<a href="https://doi.org/10.1016/j.celrep.2021.109313">10.1016/j.celrep.2021.109313</a> Venturino, A., Schulz, R., De Jesús-Cortés, H., Maes, M. E., Nagy, B., Reilly-Andújar, F., … Siegert, S. (2021). Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain. <i>Cell Reports</i>. Elsevier. <a href="https://doi.org/10.1016/j.celrep.2021.109313">https://doi.org/10.1016/j.celrep.2021.109313</a> A. Venturino, R. Schulz, H. De Jesús-Cortés, M.E. Maes, B. Nagy, F. Reilly-Andújar, G. Colombo, R.J. Cubero, F.E. Miteva, M.F. Bear, S. Siegert, Cell Reports 36 (2021). Venturino, Alessandro, Rouven Schulz, Héctor De Jesús-Cortés, Margaret E Maes, Balint Nagy, Francis Reilly-Andújar, Gloria Colombo, et al. “Microglia Enable Mature Perineuronal Nets Disassembly upon Anesthetic Ketamine Exposure or 60-Hz Light Entrainment in the Healthy Brain.” <i>Cell Reports</i>. Elsevier, 2021. <a href="https://doi.org/10.1016/j.celrep.2021.109313">https://doi.org/10.1016/j.celrep.2021.109313</a>. 96422021-07-11T22:01:16Z2026-04-03T09:46:05Z