Activation of p75NTR by proBDNF facilitates hippocampal long-term depression Academic Article uri icon


MeSH Major

  • Brain-Derived Neurotrophic Factor
  • Hippocampus
  • Long-Term Synaptic Depression
  • Protein Precursors
  • Receptors, Nerve Growth Factor


  • Pro- and mature brain-derived neurotrophic factor (BDNF) activate two distinct receptors: p75 neurotrophin receptor (p75(NTR)) and TrkB. Mature BDNF facilitates hippocampal synaptic potentiation through TrkB. Here we report that proBDNF, by activating p75(NTR), facilitates hippocampal long-term depression (LTD). Electron microscopy showed that p75(NTR) 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 p75(NTR) by proBDNF enhanced NR2B-dependent LTD and NR2B-mediated synaptic currents. These results show a crucial role for proBDNF-p75(NTR) 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.

publication date

  • August 2005



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1038/nn1510

PubMed ID

  • 16025106

Additional Document Info

start page

  • 1069

end page

  • 77


  • 8


  • 8