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Brief monocular deprivation (MD) shifts ocular dominance and reduces the density of thalamic synapses in layer 4 of the mouse primary visual cortex (V1). We found that microglial lysosome content is also increased as a result of MD. Previous studies have shown that the microglial fractalkine receptor CX3CR1 is involved in synaptic development and hippocampal plasticity.Wetherefore tested the hypothesis that neuron-to-microglial communication via CX3CR1 is an essential component of visual cortical development and plasticity in male mice. Our data show that CX3CR1 is not required for normal development of V1 responses to visual stimulation, multiple forms of experience-dependent plasticity, or the synapse loss that accompanies MD in layer 4. By ruling out an essential role for fractalkine signaling, our study narrows the search for understanding how microglia respond to active synapse modification in the visual cortex. Keywords: microglia; ocular dominance plasticity; stimulus-selective response potentiation; synaptic plasticity; visual cortex, National Institutes of Health (U.S.) (Grant R01-EY012309), National Institutes of Health (U.S.) (Grant R01-EY0237)

Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2016., Vita. Cataloged from PDF version of thesis., Includes bibliographical references (pages 151-171)., 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 extra-synaptic 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., by Rachel W. Schecter., Ph. D. in Neuroscience