Background <p>Microglia remodel neuronal circuits in pathological conditions; however, the molecular requirements for these responses and their consequences for motoneuron survival remain unclear.</p> Methods <p><i>Aif1</i> (<i>Iba1</i>) knockout mice were generated using CRISPR/Cas9-mediated deletion, and baseline phenotypes and responses to unilateral facial nerve axotomy were assessed using immunohistochemistry, transmission electron microscopy, and single-nucleus RNA sequencing of the facial motor nucleus. Motoneuron survival and nuclear γH2AX foci were evaluated 28 days post-axotomy.</p> Findings <p>Under baseline conditions, <i>Iba1</i>^{<i>−/−</i>} mice had reduced body weights and mild behavioral abnormalities compared to wild-type mice. After axotomy, microglial ensheathment of ChAT-positive facial motoneurons was reduced, with fewer neurons showing extensive perisomatic microglial coverage than in <i>Iba1</i>^<i>+/+</i> mice. Ultrastructurally, somatic synapse loss observed after injury in wild-type mice was not detected in <i>Iba1</i>^{<i>−/−</i>} mice, and fewer injured motoneurons were in contact with microglial processes. Single-nucleus transcriptomics showed an exaggerated expansion of an interferon-responsive microglial state in <i>Iba1</i>−/− mice after axotomy, whereas injured motoneurons displayed altered transcriptional programs related to synapse organization and neurotransmission. At 28 days, <i>Iba1</i>−/− mice showed reduced motoneuron survival, lower ChAT expression, and increased nuclear γH2AX foci.</p> Interpretation <p><i>Iba1</i> supports microglia-neuron cross-talk that enables effective perisomatic remodefling after axonal injury; disruption of this response is accompanied by inflammatory-state shifts and compromised motoneuron survival.</p>