Publication Type Academic Article
Authors Yang J, Harte-Hargrove L, Siao C, Marinic T, Clarke R, Ma Q, Jing D, Lafrancois J, Bath K, Mark W, Ballon D, Lee F, Scharfman H, Hempstead B
Journal Cell Rep
Volume 7
Issue 3
Pagination 796-806
Date Published 04/17/2014
ISSN 2211-1247
Keywords Brain-Derived Neurotrophic Factor, Hippocampus, Neuronal Plasticity, 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.
DOI 10.1016/j.celrep.2014.03.040
PubMed ID 24746813
PubMed Central ID PMC4118923
Back to Top