Minimally invasive protocols and quantification for microglia-mediated perineuronal net disassembly in mouse brain

Area of Science:

• Neuroscience
• Cell Biology
• Extracellular Matrix Research

Background:

• Perineuronal nets (PNNs) ensheath neurons, restricting plasticity in the adult brain.
• Chondroitinase-ABC enzyme can disassemble PNNs, but requires invasive delivery and causes prolonged extracellular matrix degradation.
• Developing less invasive and transient methods for PNN disassembly is crucial for promoting adult neural plasticity.

Purpose of the Study:

• To introduce two minimally invasive and transient protocols for PNN disassembly in the adult mouse cortex.
• To explore microglia-mediated mechanisms for PNN disassembly.
• To provide methods for analyzing PNNs within microglial endosomes-lysosomes.

Main Methods:

• Repeated administration of ketamine-xylazine-acepromazine (KXA) anesthesia in mice.
• 60-Hz light entrainment stimulation in mice.
• Analysis of PNNs within microglial endosomes-lysosomes.

Main Results:

• Both KXA anesthesia and 60-Hz light entrainment protocols successfully induced microglia-enabled PNN disassembly.
• These methods offer transient PNN disassembly, contrasting with the prolonged effects of enzymatic digestion.
• The study outlines procedures for assessing PNN degradation within microglial compartments.

Conclusions:

• Minimally invasive KXA anesthesia and light entrainment are effective strategies for transient PNN disassembly in the adult mouse cortex.
• These novel approaches facilitate microglia-mediated PNN remodeling, offering a promising alternative to enzymatic methods.
• The findings pave the way for new therapeutic strategies to enhance neural plasticity in the adult brain.