Microglial Engulfment of Multisensory Terminals in the Midbrain Inferior Colliculus During an Early Critical Period

Area of Science:

• Neuroscience
• Developmental Biology
• Cell Biology

Background:

• The lateral cortex of the inferior colliculus (LCIC) exhibits compartmental organization with distinct somatosensory and auditory inputs.
• This precise mapping develops during a critical period (birth to postnatal day 12) through a segregation process involving synaptic pruning.
• Microglial cells (MGCs) are known to eliminate unnecessary neural connections, and their dysfunction is implicated in neurodevelopmental disorders like autism spectrum disorders (ASD).

Purpose of the Study:

• To investigate the role of microglial cells (MGCs) in shaping multisensory maps within the LCIC.
• To determine if fractalkine signaling influences MGC engulfment of auditory afferents.
• To examine if MGCs phagocytose both auditory and somatosensory inputs and degrade them via the lysosomal pathway.

Main Methods:

• Utilized novel tract-tracing in living brain preparations.
• Employed immunocytochemistry in CX3CR1-GFP knock-in mice.
• Assessed microglial engulfment and lysosomal pathway activity.

Main Results:

• Demonstrated active pruning of auditory afferents by MGCs during peak LCIC projection shaping stages (postnatal days 4 and 8).
• Observed a significant decrease in auditory engulfment as the critical period closed (postnatal day 12).
• Found that MGCs engulf both auditory and somatosensory terminals, with consumed material co-localizing with the lysosomal marker CD68, independent of fractalkine signaling.

Conclusions:

• Microglia play a significant role in the remodeling and refinement of early multisensory maps in the midbrain.
• Auditory input pruning by microglia is developmentally regulated but appears independent of fractalkine signaling.
• Individual MGCs are capable of phagocytosing and degrading multisensory inputs, highlighting their crucial function in establishing neural circuits.