Journal
COMMUNICATIONS BIOLOGY
Volume 4, Issue 1, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-021-02678-x
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Funding
- Progetti di Ricerca di Rilevanza Nazionale (PRIN), Bando [2017HPTFFCPRIN]
- European Research Council (ERC) [788793-BACKUP]
- Deutsche Forschungsgemeinschaft [194101929-BL567/3-2, 44541416-TRR58-A10]
- Graduate School of Life Sciences (GSLS) Wurzburg fellowship
- Fondazione Umberto Veronesi
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Memory consolidation requires astrocytic microdomains for protein recycling, with the conversion of initially internalized proBDNF into active BDNFpro and mature BDNF enhancing synaptic re-use. This process reinforces long-term synaptic potentiation and memory retention through post-synaptic changes initiated by astrocytic BDNFpro release.
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. Beatrice Vignoli et al. examine potential molecular mechanisms of long-term storage information in mice. Their results suggest that astrocytes may help convert neuronal BDNF precursor into active prodomain and mature forms to enhance post-synaptic signaling and memory, providing further insight into the development of memory circuits.
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