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Vignoli, Beatrice; Sansevero, Gabriele; Sasi, Manju; Rimondini, Roberto; Blum, Robert; Bonaldo, Valerio; Biasini, Emiliano; Santi, Spartaco; Berardi, Nicoletta; Lu, Bai; Canossa, Marco
Communications biology, 10/2021, Letnik: 4, Številka: 1Journal Article
Memory consolidation requires astrocytic microdomains for protein recycling; but whether this lays a mechanistic foundation for long-term information storage remains enigmatic. Here we demonstrate that persistent synaptic strengthening invited astrocytic microdomains to convert initially internalized (pro)-brain-derived neurotrophic factor (proBDNF) into active prodomain (BDNFpro) and mature BDNF (mBDNF) for synaptic re-use. While mBDNF activates TrkB, we uncovered a previously unsuspected function for the cleaved BDNFpro, which increases TrkB/SorCS2 receptor complex at post-synaptic sites. Astrocytic BDNFpro release reinforced TrkB phosphorylation to sustain long-term synaptic potentiation and to retain memory in the novel object recognition behavioral test. Thus, the switch from one inactive state to a multi-functional one of the proBDNF provides post-synaptic changes that survive the initial activation. This molecular asset confines local information storage in astrocytic microdomains to selectively support memory circuits.
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