Integrity of neural extracellular matrix is required for microglia-mediated synaptic remodeling

Area of Science:

• Neuroscience
• Cell Biology
• Extracellular Matrix Research

Background:

• Microglia are key players in synaptic remodeling, a process influenced by the neural extracellular matrix (ECM).
• The precise mechanisms governing microglial-mediated synaptic remodeling and the ECM's role remain largely unknown.

Purpose of the Study:

• To investigate the impact of the neural ECM on microglial synaptic remodeling.
• To elucidate how ECM integrity influences microglial interactions with synapses.

Main Methods:

• Disruption of ECM integrity in the mouse retrosplenial cortex using chondroitinase ABC (ChABC).
• In vivo two-photon microscopy to observe microglial dynamics and synaptic structures.
• Assessment of synaptic remodeling following induced synaptic stress (photodamage).

Main Results:

• ChABC treatment enhanced microglial branching complexity and ECM phagocytosis while reducing basal spine elimination.
• ECM attenuation significantly inhibited synaptic remodeling after photodamage-induced stress.
• Observed changes included less stable microglial contacts, reduced complement protein deposition (calreticulin, C1q, C3), and impaired CR3 receptor expression.

Conclusions:

• The neural ECM plays a critical role in regulating microglial synaptic remodeling.
• ECM integrity influences complement protein deposition at synapses, impacting microglial function.
• Findings offer new insights into the interplay between ECM, microglia, and synaptic plasticity.