Nature Neuroscience
8, 1069 - 1077 (2005)
Published online: 17 July 2005; | doi:10.1038/nn1510
Activation of p75NTR by proBDNF facilitates hippocampal long-term depressionNewton H Woo1, Henry K Teng2, Chia-Jen Siao2, Cristina Chiaruttini1, Petti T Pang1, Teresa A Milner3, Barbara L Hempstead2
& Bai Lu11
Section on Neural Development and Plasticity, LCSN, NICHD, Porter Neuroscience Research Center, 35 Lincoln Drive, Bethesda, Maryland 20892-3714, USA. 2
Division of Hematology, Department of Medicine, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA. 3
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 411 East 69th Street, New York, New York 10021, USA.
Correspondence should be addressed to Bai Lu bailu@mail.nih.gov Pro- and mature brain-derived neurotrophic factor (BDNF) activate two distinct receptors: p75 neurotrophin receptor (p75NTR) and TrkB. Mature BDNF facilitates hippocampal synaptic potentiation through TrkB. Here we report that proBDNF, by activating p75NTR, facilitates hippocampal long-term depression (LTD). Electron microscopy showed that p75NTR localized in dendritic spines, in addition to afferent terminals, of CA1 neurons. Deletion of p75
NTR in mice selectively impaired the NMDA receptor−dependent LTD, without affecting other forms of synaptic plasticity. p75
NTR-/- mice also showed a decrease in the expression of NR2B, an NMDA receptor subunit uniquely involved in LTD. Activation of p75NTR by proBDNF enhanced NR2B-dependent LTD and NR2B-mediated synaptic currents. These results show a crucial role for proBDNF-p75NTR signaling in LTD and its potential mechanism, and together with the finding that mature BDNF promotes synaptic potentiation, suggest a bidirectional regulation of synaptic plasticity by proBDNF and mature BDNF.
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