Title | proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Yang 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 |
Journal | Cell Rep |
Volume | 7 |
Issue | 3 |
Pagination | 796-806 |
Date Published | 2014 May 08 |
ISSN | 2211-1247 |
Keywords | Alleles, 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. |
DOI | 10.1016/j.celrep.2014.03.040 |
Alternate Journal | Cell Rep |
PubMed ID | 24746813 |
PubMed Central ID | PMC4118923 |
Grant List | T32 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)