Changes in the sensory experience of an animal shapes behavior through synaptic plasticity. Modification in the strength of synaptic drive can result from adjustments in the strength of existing synapses, creation of new synapses, or removal of existing ones and involves presynaptic, postsynaptic, and extrasynaptic mechanisms. Ocular dominance (OD) plasticity following brief periods of monocular deprivation (MD) is a classic example of experience-dependent change, which leads to a rapid weakening of cortical responsiveness to the deprived eye and a strengthening of responsiveness to the non-deprived eye. Though there is clear anatomical reorganization following long periods of lid suture, only recently has brief periods (3 days) of MD has been shown to drive structural plasticity of thalamic input to binocular visual cortex. The exact molecular and synaptic mechanisms responsible for rapid OD shifts remain unclear. In my thesis work, I address the requirement of proper microglial functioning via the fractalkine receptor (CX3CR1) in OD plasticity following 3 days of MD. I first identify increased lysosomal content in microglia within layer 4 (L4) of binocular visual cortex following MD, which suggests microglia participate in this structural rearrangement. As it is currently believed that a major axis of communication between neurons and microglia occurs via fractalkine and its specific receptor CX3CR1, I investigated OD plasticity within the CX3CR1 KO mouse. My experiments reveal increased lysosomal content, structural plasticity of thalamocortical synapses, and OD shifts measured with visually evoked potentials (VEPs) all occur normally in this mutant mouse as a result of 3 days of MD with only subtle differences when compared to WT mice. I conclude that, while microglia may have a role in the anatomical and functional experience-dependent cortical plasticity driven by brief lid suture, it does not require CX3CR1.