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Updated: Aug 16, 2026

Assessment of Dendritic Arborization in the Dentate Gyrus of the Hippocampal Region in Mice
Published on: March 31, 2015
Activation of p75NTR by proBDNF facilitates hippocampal long-term depression
Newton H Woo1, Henry K Teng, Chia-Jen Siao
1Section on Neural Development and Plasticity, LCSN, NICHD, Porter Neuroscience Research Center, 35 Lincoln Drive, Bethesda, Maryland 20892-3714, USA.
Abstract:
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.
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