Activation of p75NTR by proBDNF facilitates hippocampal long-term depression.
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.
Woo
Newton H
NH
Section on Neural Development and Plasticity, LCSN, NICHD, Porter Neuroscience Research Center, 35 Lincoln Drive, Bethesda, Maryland 20892-3714, USA.
Teng
Henry K
HK
Siao
Chia-Jen
CJ
Chiaruttini
Cristina
C
Pang
Petti T
PT
Milner
Teresa A
TA
Hempstead
Barbara L
BL
Lu
Bai
B
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D066298:In Vitro Techniques; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009411:Nerve Endings / Q000378:metabolism / Q000648:ultrastructure; D011498:Protein Precursors / Q000494:pharmacology*; D020800:Receptor, Nerve Growth Factor; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000172:deficiency / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; C121001:NR2B NMDA receptor; D011498:Protein Precursors; D020800:Receptor, Nerve Growth Factor; D016194:Receptors, N-Methyl-D-Aspartate; D017475:Receptors, Nerve Growth Factor