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

Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain.
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DOI:
10.1016/j.celrep.2021.109313
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发表时间:
2021-07-06
期刊:
影响因子:
8.8
通讯作者:
Siegert S
Siegert S
中科院分区:
生物学1区
文献类型:
--
作者:
Venturino A;Schulz R;De Jesús-Cortés H;Maes ME;Nagy B;Reilly-Andújar F;Colombo G;Cubero RJA;Schoot Uiterkamp FE;Bear MF;Siegert S

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Perineuronal nets (PNN) are a component of the extracellular matrix that 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 behavior impact. 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 as 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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