Synaptic Refinement in the Developing Retinogeniculate System

Classical complement cascade proteins mediate synaptic refinement in the developing retinogeniculate system. During the first postnatal week, overlapping inputs from both eyes (red versus green inputs) segregate into eye-specific territories in the dorsal lateral geniculate nucleus (dLGN) of the thalamus, resulting in the termination of ipsilateral (Ipsi) and contralateral (Contra) retinal ganglion cell (RGC) inputs in distinct nonoverlapping domains in the mature dLGN (Left panel). Eye-specific segregation involves the selective local pruning of overlapping parts of axonal arbors and the elaboration of the appropriate eye inputs to form the adult pattern of connections. A given relay neuron in the dLGN will ultimately receive 1–2 mature inputs from either the left or right eye (neuron, bottom left). Right panel: Mice deficient in classical complement cascade components, C1q and C3, and the microglia-specific complement receptor 3 (CR3) have sustained defects in eye-specific segregation compared with wild-type (WT) animals (topright), depicted as increased overlap of ipsi- and contralateral RGC inputs in the dLGN (yellow region) and presence of binocularly innervated dLGN relay neurons (bottomright) (Stephan et al., Annu. Rev. Neurosci. 2012).