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

Abstract

The lateral cortex of the inferior colliculus (LCIC) receives multisensory input arrays that preferentially target its compartmental organization. Inputs of somatosensory origin end within modular zones, while auditory inputs terminate throughout an encompassing matrix. Such discrete mapping emerges during an early postnatal critical period (birth to postnatal day 12, P12) via a process of segregation. Similar to other primitive brain maps, it appears an initial excess of connections may be pruned through a refinement process. Microglial cells (MGCs) are involved in a variety of systems in the selective removal and degradation of unnecessary contacts. Aberrations in map plasticity during early critical periods have been associated with certain neurodevelopmental conditions, including autism spectrum disorders (ASD). Despite evidence linking multisensory integration deficits with cognitive/behavioral disturbances associated with ASD, mechanisms that govern multimodal network modifications remain poorly understood. Thus, the present study combines novel tract-tracing approaches in living brain preparations and immunocytochemistry in CX3CR1-GFP knock-in mice to determine: (1) if fractalkine signaling (CX3CL1–CX3CR1) influences MGC engulfment of auditory afferents, (2) whether individual MGCs phagocytose endings of multisensory origin (auditory and somatosensory), and (3) whether consumed product is degraded via the MGC's lysosomal pathway. We demonstrate active MGC pruning of auditory endings at peak LCIC stages for projection shaping (P4, P8) that significantly decreases coincident with its critical period closure (P12). While developmentally regulated, auditory engulfment appears fractalkine signaling-independent. We also provide evidence that individual LCIC microglia engulf both auditory and somatosensory terminals that co-localize with the lysosomal marker, CD68. These results suggest a prominent role for microglia in the remodeling of early multisensory midbrain maps.