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

Autor: Venturino A; Institute of Science and Technology (IST) Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Schulz R; Institute of Science and Technology (IST) Austria, Am Campus 1, 3400 Klosterneuburg, Austria., De Jesús-Cortés H; The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Maes ME; Institute of Science and Technology (IST) Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Nagy B; Institute of Science and Technology (IST) Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Reilly-Andújar F; The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Colombo G; Institute of Science and Technology (IST) Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Cubero RJA; Institute of Science and Technology (IST) Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Schoot Uiterkamp FE; Institute of Science and Technology (IST) Austria, Am Campus 1, 3400 Klosterneuburg, Austria., Bear MF; The Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Siegert S; Institute of Science and Technology (IST) Austria, Am Campus 1, 3400 Klosterneuburg, Austria. Electronic address: sandra.siegert@ist.ac.at.
Jazyk: angličtina
Zdroj: Cell reports [Cell Rep] 2021 Jul 06; Vol. 36 (1), pp. 109313.
DOI: 10.1016/j.celrep.2021.109313
Abstrakt: 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.
Competing Interests: Declaration of interests The authors declare no competing interests. A.V. and S.S. disclose an international patent application (PCT/EP2020/079365).
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE