Repopulating microglia recapitulate developmental characteristics during a period of auditory circuit recovery.

Precision in auditory brainstem circuitry is essential for sound localization and higher levels of processing. Assembly of this circuitry requires specialized developmental mechanisms, including multipartite signaling between neurons and glia. Microglia populate the developing auditory brainstem nuclei lateromedially, appearing first in the ventral cochlear nucleus, and later in the medial nucleus of the trapezoid body. Microglia increase in number just after hearing onset, then reduce to stable levels following a period of synaptic refinement. We previously showed that early microglia depletion impaired synaptic pruning and auditory brainstem responses. Microglial repopulation, which occurred significantly later than normal development, restored these deficits. This finding suggests that microglia take on developmental roles to reinstate circuit assembly outside of the normal development timeframe. To begin unravelling this phenomenon, we compared morphology and phagocytosis in developing and repopulating microglia. We used CX3CR1+/EGFP mice and characterized individual microglia throughout the postnatal period in control mice and in mice with repopulating microglia. We tested whether repopulating microglia recapitulate developmental qualities by measuring microglial surface area, volume, branching, and lysosomes. We found that infiltrating microglia acquire developmental properties during synaptic refinement, even beyond the normal auditory development timeframe.