Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain
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Published version
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Author(s) • • • • • • • • •
Venturino, Alessandro
Schulz, Rouven
De Jesús-Cortés, Héctor
Maes, Margaret E
Nagy, Bálint
Reilly-Andújar, Francis
Colombo, Gloria
Cubero, Ryan John A
Schoot Uiterkamp, Florianne E
Bear, Mark F
Date Issued
July 2021
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Venturino, Alessandro, Schulz, Rouven, De Jesús-Cortés, Héctor, Maes, Margaret E, Nagy, Bálint et al. 2021. "Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain." Cell Reports, 36 (1).
Version
Final published version
Abstract
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.
MIT Department
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1016/j.celrep.2021.109313