Hippocampal neurons recycle BDNF for activity-dependent secretion and LTP maintenance.
Regulation of brain-derived neurotrophic factor (BDNF) secretion plays a critical role in long-term potentiation (LTP). It is generally thought that the supply for this secretion is newly synthesized BDNF targeted to the synapse. Here we provide evidence that hippocampal neurons additionally recycle BDNF for activity-dependent secretion. Exogenously applied BDNF is internalized by cultured neurons and rapidly becomes available for activity-dependent secretion, which is controlled by the same mechanisms that regulate the secretion of newly synthesized BDNF. Moreover, BDNF recycling replaced the new synthesis pathway in mediating the maintenance of LTP in hippocampal slices: the late phase LTP, which is abolished by protein synthesis inhibition, was rescued in slices preincubated with BDNF. Thus, endocytosed BDNF is fed back to the activity-dependent releasable pool required for LTP maintenance.
Santi
Spartaco
S
CNR-ITOI/ISMN, Bologna, Italy.
Cappello
Silvia
S
Riccio
Massimo
M
Bergami
Matteo
M
Aicardi
Giorgio
G
Schenk
Ursula
U
Matteoli
Michela
M
Canossa
Marco
M
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D004705:Endocytosis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D011500:Protein Synthesis Inhibitors; D000841:Anisomycin; D020813:Receptor, trkB