The article "The Classical Complement Cascade Mediates CNS Synapse Elimination" explores the role of the classical complement cascade in the development of neural circuits by eliminating inappropriate synaptic connections. During development, the formation of mature neural circuits requires the selective elimination of synapses that are not needed. The study identifies C1q, the initiating protein of the classical complement cascade, as being expressed by postnatal neurons in response to immature astrocytes and localized to synapses throughout the postnatal central nervous system (CNS) and retina. Mice deficient in C1q or the downstream complement protein C3 exhibit significant defects in CNS synapse elimination, as shown by the failure of anatomical refinement of retinogeniculate connections and the retention of excess retinal innervation by lateral geniculate neurons. Neuronal C1q is normally downregulated in the adult CNS, but in a mouse model of glaucoma, C1q becomes upregulated and synaptically relocalized in the adult retina early in the disease. These findings support a model in which unwanted synapses are tagged by complement for elimination and suggest that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative disease. The study also shows that C1q is localized to synapses in the developing CNS and that the complement cascade is involved in synaptic elimination. The findings have important implications for understanding the mechanism of synapse loss in neurodegenerative disease, as the normal developmental mechanism of complement-mediated synapse elimination becomes aberrantly reactivated in the adult CNS after injury or neurodegenerative disease. The study also highlights the role of astrocytes and the classical complement cascade in mediating CNS synapse elimination in the retinogeniculate pathway. The findings suggest that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative diseases such as glaucoma.The article "The Classical Complement Cascade Mediates CNS Synapse Elimination" explores the role of the classical complement cascade in the development of neural circuits by eliminating inappropriate synaptic connections. During development, the formation of mature neural circuits requires the selective elimination of synapses that are not needed. The study identifies C1q, the initiating protein of the classical complement cascade, as being expressed by postnatal neurons in response to immature astrocytes and localized to synapses throughout the postnatal central nervous system (CNS) and retina. Mice deficient in C1q or the downstream complement protein C3 exhibit significant defects in CNS synapse elimination, as shown by the failure of anatomical refinement of retinogeniculate connections and the retention of excess retinal innervation by lateral geniculate neurons. Neuronal C1q is normally downregulated in the adult CNS, but in a mouse model of glaucoma, C1q becomes upregulated and synaptically relocalized in the adult retina early in the disease. These findings support a model in which unwanted synapses are tagged by complement for elimination and suggest that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative disease. The study also shows that C1q is localized to synapses in the developing CNS and that the complement cascade is involved in synaptic elimination. The findings have important implications for understanding the mechanism of synapse loss in neurodegenerative disease, as the normal developmental mechanism of complement-mediated synapse elimination becomes aberrantly reactivated in the adult CNS after injury or neurodegenerative disease. The study also highlights the role of astrocytes and the classical complement cascade in mediating CNS synapse elimination in the retinogeniculate pathway. The findings suggest that complement-mediated synapse elimination may become aberrantly reactivated in neurodegenerative diseases such as glaucoma.