Compromised fractalkine signaling delays microglial occupancy of emerging modules in the multisensory midbrain

Microglial cells (MGCs) are highly dynamic and have been implicated in shaping discrete neural maps in several unimodal systems. MGCs respond to numerous cues in their microenvironment, including the neuronally expressed chemokine, fractalkine (CX3CL1), via interactions with its corresponding fractalkine receptor (CX3CR1). The present study examines microglial and CX3CL1 patterns with regard to the emerging modular‐extramodular matrix organization within the lateral cortex of the inferior colliculus (LCIC). The LCIC is a multisensory shell region of the midbrain inferior colliculus where discrete compartments receive modality‐specific connections. Somatosensory inputs terminate within modular confines, while auditory inputs target the surrounding matrix. Glutamic acid decarboxylase (GAD) is an established marker of LCIC modules in developing mouse. During early postnatal development, multimodal LCIC afferents segregate into discrete, neurochemically defined compartments. Here, we analyzed neonatal GAD67‐GFP (GFP is defined as green fluorescent protein) and CX3CR1‐GFP mice to assess: (1) whether MGCs are recruited to distinct LCIC compartments known to be undergoing active circuit assembly, and (2) if such behaviors are fractalkine signaling‐dependent. MGCs colonize the nascent LCIC by birth and increase in density until postnatal day 12 (P12). At the peak critical period (P4‐P8), MGCs conspicuously border emerging LCIC modules, prior to their subsequent invasion by P12. CX3CL1 expression becomes distinctly modular at P12, in keeping with the notion of fractalkine‐mediated recruitment of microglia to modular centers. In CX3CR1GFP/GFP mice with compromised fractalkine signaling, microglial recruitment into modules is delayed. Taken together, these results suggest a potential role for microglia and fractalkine signaling in sculpting multisensory LCIC maps during an early critical period. Main Points Fractalkine signaling (CX3CL1‐CX3CR1) influences microglia recruitment into the multimodal midbrain during an early critical period. Compartmental fractalkine (CX3CL1) expression signals microglial entry, which is delayed in CX3CR1‐deficient mice.