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  • Astrocytic microdomains from mouse cortex gain molecular control over long-term information storage and memory retention.

Astrocytic microdomains from mouse cortex gain molecular control over long-term information storage and memory retention.

Communications biology (2021-10-07)
Beatrice Vignoli, Gabriele Sansevero, Manju Sasi, Roberto Rimondini, Robert Blum, Valerio Bonaldo, Emiliano Biasini, Spartaco Santi, Nicoletta Berardi, Bai Lu, Marco Canossa
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Brain Derived Neurotrophic Factor Antibody, pro, Chemicon®, from chicken
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DAPI, for nucleic acid staining
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Poly-L-lysine hydrobromide, mol wt 70,000-150,000, lyophilized powder, γ-irradiated, BioXtra, suitable for cell culture
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Duolink® In Situ PLA® Probe Anti-Goat MINUS, Affinity purified Donkey anti-Goat IgG (H+L)
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Duolink® In Situ PLA® Probe Anti-Rabbit PLUS, Affinity purified Donkey anti-Rabbit IgG (H+L)
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Tamoxifen, ≥99%
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Anti-Post Synaptic Density Protein 95 Antibody, clone 6G6-1C9, clone 6G6-1C9, Chemicon®, from mouse
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Anti-NeuN Antibody, serum, from guinea pig