Abstract
After peripheral nerve injury, the structure of the spinal cord is actively regulated by glial cells, contributing to the chronicity of neuropathic pain. However, the mechanism by which peripheral nerve injury leads to synaptic imbalance remains elusive. Here, we use a pH-reporter system and find that nerve injury triggers a reorganization of excitatory synapses that is influenced by the accumulation of the ganglioside GT1b at afferent terminals. GT1b acts as a protective signal against nerve injury-induced spinal synapse elimination. Inhibition of GT1b-synthesis increases glial phagocytosis of excitatory pre-synapses and reduces excitatory synapses post-injury. In vitro analyses reveal a positive correlation between GT1b accumulation and the frequency of pre-synaptic calcium activity, with GT1b-mediated suppression of glial phagocytosis occurring through SYK dephosphorylation. Our study highlights GT1b's pivotal role in preventing synapse elimination after nerve injury and offers new insight into the molecular underpinning of activity-dependent synaptic stability and glial phagocytosis.