Microglia and fractalkine involvement in shaping multimodal midbrain circuitry

Microglial cells (MGCs) are highly dynamic and have been implicated in shaping discrete neural maps in several systems. MGCs respond to numerous cues in their microenvironment, including a neuronally-expressed chemokine, CX3CL1 (fractalkine). The present study examines microglial and CX3CL1 patterns with regard to the emerging modular-extramodular framework within the lateral cortex of the inferior colliculus (LCIC). The LCIC is a shell region of the auditory midbrain where discrete compartments receive modality-specific connections, whereby somatosensory inputs terminate within modules and auditory inputs target surrounding extramodular zones. A reliable modular marker, glutamic acid decarboxylase (GAD), enables visualization of emerging modular domains in the nascent mouse LCIC. Developing multimodal connectivity patterns interface with its neurochemically-defined patch/matrix-like organization. A developmental series of postnatal GAD67-GFP and CX3CR1-GFP mice were utilized to explore the potential involvement of MGCs and role of fractalkine signaling in establishing LCIC functional compartments. MGCs occupy the neonatal LCIC at birth, with spatial heterogeneities and densities that change with age and respect to the modular-extramodular framework and its segregating multimodal afferents. MGCs conspicuously border modular-extramodular boundaries at P4-P8 prior to invading modular confines by P12. CX3CL1 labeling is clearly modular at P12, in keeping with the notion of fractalkine-mediated recruitment of microglia to modular centers. CX3CR1GFP/GFP results suggest microglial movement into modules is delayed due to compromised fractalkine signaling. Ongoing experiments aim to further elucidate the role of MGCs and fractalkine signaling in refining multisensory LCIC compartments during an early critical period