Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain

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...

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Main Authors: 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, Siegert, Sandra
Other Authors: Picower Institute for Learning and Memory
Format: Article
Language:English
Published: Elsevier BV 2021
Online Access:https://hdl.handle.net/1721.1/138161
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author 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
Siegert, Sandra
author2 Picower Institute for Learning and Memory
author_facet Picower Institute for Learning and Memory
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
Siegert, Sandra
author_sort Venturino, Alessandro
collection MIT
description 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.
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spelling mit-1721.1/1381612023-08-07T18:11:16Z Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain 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 Siegert, Sandra Picower Institute for Learning and Memory Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences 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. 2021-11-19T15:25:50Z 2021-11-19T15:25:50Z 2021-07 2021-11-19T15:21:24Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/138161 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). en 10.1016/j.celrep.2021.109313 Cell Reports Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Elsevier BV Elsevier
spellingShingle 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
Siegert, Sandra
Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain
title Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain
title_full Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain
title_fullStr Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain
title_full_unstemmed Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain
title_short Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain
title_sort microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60 hz light entrainment in the healthy brain
url https://hdl.handle.net/1721.1/138161
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