proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus.

TitleproBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus.
Publication TypeJournal Article
Year of Publication2014
AuthorsYang J, Harte-Hargrove LC, Siao C-J, Marinic T, Clarke R, Ma Q, Jing D, Lafrancois JJ, Bath KG, Mark W, Ballon D, Lee FS, Scharfman HE, Hempstead BL
JournalCell Rep
Volume7
Issue3
Pagination796-806
Date Published2014 May 08
ISSN2211-1247
KeywordsAlleles, Animals, Brain-Derived Neurotrophic Factor, Cells, Cultured, Gene Knock-In Techniques, Hippocampus, Long-Term Synaptic Depression, Mice, Neuronal Plasticity, Protein Binding, Protein Precursors, Receptor, trkB, Receptors, Nerve Growth Factor, Recombinant Fusion Proteins, Synaptic Transmission
Abstract

Experience-dependent plasticity shapes postnatal development of neural circuits, but the mechanisms that refine dendritic arbors, remodel spines, and impair synaptic activity are poorly understood. Mature brain-derived neurotrophic factor (BDNF) modulates neuronal morphology and synaptic plasticity, including long-term potentiation (LTP) via TrkB activation. BDNF is initially translated as proBDNF, which binds p75(NTR). In vitro, recombinant proBDNF modulates neuronal structure and alters hippocampal long-term plasticity, but the actions of endogenously expressed proBDNF are unclear. Therefore, we generated a cleavage-resistant probdnf knockin mouse. Our results demonstrate that proBDNF negatively regulates hippocampal dendritic complexity and spine density through p75(NTR). Hippocampal slices from probdnf mice exhibit depressed synaptic transmission, impaired LTP, and enhanced long-term depression (LTD) in area CA1. These results suggest that proBDNF acts in vivo as a biologically active factor that regulates hippocampal structure, synaptic transmission, and plasticity, effects that are distinct from those of mature BDNF.

DOI10.1016/j.celrep.2014.03.040
Alternate JournalCell Rep
PubMed ID24746813
PubMed Central IDPMC4118923
Grant ListT32 MH067763 / MH / NIMH NIH HHS / United States
P01 HD023315 / HD / NICHD NIH HHS / United States
R01 NS064114 / NS / NINDS NIH HHS / United States
R01 NS037562 / NS / NINDS NIH HHS / United States
NS030627 / NS / NINDS NIH HHS / United States
R01 NS052819 / NS / NINDS NIH HHS / United States
T32 MH097763 / MH / NIMH NIH HHS / United States
HD23315 / HD / NICHD NIH HHS / United States
R01 NS030687 / NS / NINDS NIH HHS / United States
NS37562 / NS / NINDS NIH HHS / United States
NS064114 / NS / NINDS NIH HHS / United States
NS052819 / NS / NINDS NIH HHS / United States
Related Institute: 
MRI Research Institute (MRIRI)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065