Neuronal membrane proteasomes regulate neuronal circuit activity in vivo and are required for learning-induced behavioral plasticity br

Protein degradation is critical for brain function through processes that remain incom-pletely understood. Here, we investigated the in vivo function of the 20S neuronal membrane proteasome (NMP) in the brain of Xenopus laevis tadpoles. With biochem-istry, immunohistochemistry, and electron microscopy, we demonstrated that NMPs are conserved in the tadpole brain and preferentially degrade neuronal activity-induced newly synthesized proteins in vivo. Using in vivo calcium imaging in the optic tectum, we showed that acute NMP inhibition rapidly increased spontaneous neuronal activity, resulting in hypersynchronization across tectal neurons. At the circuit level, inhibiting NMPs abolished learning-dependent improvement in visuomotor behavior in live ani-mals and caused a significant deterioration in basal behavioral performance following visual training with enhanced visual experience. Our data provide in vivo character-ization of NMP functions in the vertebrate nervous system and suggest that NMP-mediated degradation of activity-induced nascent proteins may serve as a homeostatic modulatory mechanism in neurons that is critical for regulating neuronal activity and experience-dependent circuit plasticity

Automated summary

Protein degradation by the neuronal membrane proteasome (NMP) is crucial for brain function. It selectively degrades newly synthesized proteins induced by neuronal activity and plays a role in regulating neuronal activity and experience-dependent circuit plasticity.