Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Cell reports (Cambridge), 2021-07, Vol.36 (1), p.109313-109313, Article 109313

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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. [Display omitted] •Repeated ketamine anesthesia induces perineuronal net loss•PNN loss reinstates juvenile-like ocular dominance plasticity•Microglia interact with parvalbumin neurons and remodel PNN•60-Hz light stimulation recapitulates ketamine-induced PNN loss Venturino et al. show that repeated ketamine anesthesia results in perineuronal net loss, which promotes juvenile-like, ocular-dominance plasticity in adult mice. Microglia are key players in the PNN disassembly, in which 60-Hz light entrainment reproduces that phenotype, providing an alternative, non-invasive strategy to remodel PNNs.