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Proc Natl Acad Sci U S A 2023 Jan 17;1203:e2216537120. doi: 10.1073/pnas.2216537120.
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Neuronal membrane proteasomes regulate neuronal circuit activity in vivo and are required for learning-induced behavioral plasticity.

He HY , Ahsan A , Bera R , McLain N , Faulkner R , Ramachandran KV , Margolis SS , Cline HT .

Protein degradation is critical for brain function through processes that remain incompletely understood. Here, we investigated the in vivo function of the 20S neuronal membrane proteasome (NMP) in the brain of Xenopus laevis tadpoles. With biochemistry, 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 animals and caused a significant deterioration in basal behavioral performance following visual training with enhanced visual experience. Our data provide in vivo characterization 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.

PubMed ID: 36630455
PMC ID: PMC9934054
Article link: Proc Natl Acad Sci U S A

Species referenced: Xenopus laevis
Genes referenced: avd camk2a cbl npl psmd2 ran sncb
Antibodies: CaMK2a Ab4 GFP Ab1

Article Images: [+] show captions
References [+] :
Abraham, Metaplasticity: tuning synapses and networks for plasticity. 2008, Pubmed