Mechanisms of Microglia-Synapse Interactions in Visual System Development and Plasticity

Abstract

Microglia and immune genes are required for the proper development and plasticity of the mouse visual system. Microglia, the resident macrophages of the brain parenchyma, promote developmental synapse elimination by engulfing synapses, and many genes originally identified through their contributions to immunity are important for visual system development and plasticity. The mechanisms underlying microglia and immune gene interactions with developing synapses are, however, poorly understood. We therefore assessed the contributions of three different immune signaling pathways to synaptic development in the mouse visual system. We first tested in vitro and in vivo strategies for studying microglial synapse engulfment. We developed an in vitro engulfment assay, and used it to elucidate signaling between the neuronal ligand CD47 and the microglial receptor SIRPα. We next investigated whether the pro- engulfment classical complement cascade is required for ocular dominance plasticity, by examining aspects of binocular visual cortex development and plasticity in mice lacking C1q. Surprisingly, we found that visual cortex is mostly normal in the absence of C1q, with only mild, experience-dependent synaptic phenotypes detectable in these animals. Finally, we studied whether CD200, an immune-suppressant protein expressed in many tissues including the brain, is required for proper retinogeniculate refinement. In contrast to previous results, we were not able to detect a refinement phenotype in mice lacking CD200. Together, these results illustrate the complexity of the molecular mechanisms underlying immune system contributions to visual system development and plasticity.