Where No Synapses Go: Gatekeepers of Circuit Remodeling and Synaptic Strength

摘要

Growth inhibitory molecules in the adult mammalian CNS have been implicated in blocking axonal sprouting and regeneration following injury. Prominent CNS regeneration inhibitors include Nogo-A, OMgp and CSPGs, and a key question concerns their physiological role in the naïve CNS. Emerging evidence suggests novel functions in dendrites and at synapses of glutamatergic neurons. CNS regeneration inhibitors target the neuronal actin cytoskeleton to regulate dendritic spine maturation, long-term synapse stability, and Hebbian forms of synaptic plasticity. This is accomplished in part by antagonizing plasticity-promoting signaling pathways activated by neurotrophic factors. Altered function of CNS regeneration inhibitors is associated with mental illness and loss of long-lasting memory, suggesting unexpected and novel physiological roles for these molecules in brain health.