title: Peri-Synaptic Glia Recycles Brain-Derived Neurotrophic Factor for LTP Stabilization and Memory Retention.
abstract: Glial cells respond to neuronal activation and release neuroactive molecules (termed "gliotransmitters") that can affect synaptic activity and modulate plasticity. In this study, we used molecular genetic tools, ultra-structural microscopy, and electrophysiology to assess the role of brain-derived neurotrophic factor (BDNF) on cortical gliotransmission in vivo. We find that glial cells recycle BDNF that was previously secreted by neurons as pro-neurotrophin following long-term potentiation (LTP)-inducing electrical stimulation. Upon BDNF glial recycling, we observed tight, temporal, highly localized TrkB phosphorylation on adjacent neurons, a process required to sustain LTP. Engagement of BDNF recycling by astrocytes represents a novel mechanism by which cortical synapses can expand BDNF action and provide synaptic changes that are relevant for the acquisition of new memories. Accordingly, mice deficient in BDNF glial recycling fail to recognize familiar from novel objects, indicating a physiological requirement for this process in memory consolidation.
authors.affiliation: European Brain Research Institute (EBRI) "Rita Levi-Montalcini", via del Fosso di Fiorano 64, 00143 Rome, Italy; Centre for Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Povo (TN), Italy. Electronic address: beatrice.vignoli@unitn.it.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Vignoli
authors.affiliation: Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, via San Donato 15, 40127 Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Battistini
authors.affiliation: National Research Council (CNR), Institute of Neuroscience, via Moruzzi 1, 56100 Pisa, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Melani
authors.affiliation: Institute for Clinical Neurobiology, University Hospital, Julius Maximilians University, Versbacher Straße 5, 97078 Würzburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Blum
authors.affiliation: National Research Council (CNR), Institute of Molecular Genetics (IGM), Laboratory of Muscoloskeletal Cell Biology, IOR, via di Barbiano1/10, 40136 Bologna, Italy.
authors.forename: Spartaco
authors.initials: S
authors.lastname: Santi
authors.affiliation: National Research Council (CNR), Institute of Neuroscience, via Moruzzi 1, 56100 Pisa, Italy; Department of Neuroscience, Psychology, Drug Research, and Child Health (NEUROFARBA), University of Florence, via di San Salvi 26, 50100 Florence, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Berardi
authors.affiliation: European Brain Research Institute (EBRI) "Rita Levi-Montalcini", via del Fosso di Fiorano 64, 00143 Rome, Italy; Centre for Integrative Biology (CIBIO), University of Trento, via Sommarive 9, 38123 Povo (TN), Italy. Electronic address: marco.canossa@unitn.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Canossa
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D017774:Long-Term Potentiation; D008568:Memory; D051379:Mice; D009457:Neuroglia / Q000378:metabolism*; D010766:Phosphorylation; D020813:Receptor, trkB / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; D020813:Receptor, trkB