A BDNF-Mediated Push-Pull Plasticity Mechanism for Synaptic Clustering

Dragos Niculescu, Kristin Michaelsen-Preusse, Ülkü Güner, René van Dorland, Corette J. Wierenga, Christian Lohmann*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


During development, activity-dependent synaptic plasticity refines neuronal networks with high precision. For example, spontaneous activity helps sorting synaptic inputs with similar activity patterns into clusters to enhance neuronal computations in the mature brain. Here, we show that TrkB activation and postsynaptic brain-derived neurotrophic factor (BDNF) are required for synaptic clustering in developing hippocampal neurons. Moreover, BDNF and TrkB modulate transmission at synapses depending on their clustering state, indicating that endogenous BDNF/TrkB signaling stabilizes locally synchronized synapses. Together with our previous data on proBDNF/p75NTR signaling, these findings suggest a push-pull plasticity mechanism for synaptic clustering: BDNF stabilizes clustered synapses while proBDNF downregulates out-of-sync synapses. This idea is supported by our observation that synaptic clustering requires matrix-metalloproteinase-9 activity, a proBDNF-to-BDNF converting enzyme. Finally, NMDA receptor activation mediates out-of-sync depression upstream of proBDNF signaling. Together, these data delineate an efficient plasticity mechanism where proBDNF and mature BDNF establish synaptic clustering through antagonistic modulation of synaptic transmission. Niculescu et al. found that synaptic clustering requires BDNF/TrkB signaling, activity of the proBDNF-to-BDNF conversion enzyme MMP9, and NMDA receptor activation. Their study delineates a push-pull plasticity mechanism where BDNF stabilizes clustered synapses while its precursor, proBDNF, depresses unclustered synapses, together ensuring robust clustering of synaptic inputs in developing neurons.

Original languageEnglish
Pages (from-to)2063-2074
Number of pages12
JournalCell Reports
Issue number8
Publication statusPublished - 21 Aug 2018

Bibliographical note

Available online 24 August 2018


  • BDNF
  • development
  • hippocampus
  • MMP9
  • postsynaptic
  • proBDNF
  • synaptic clustering
  • TrkB


Dive into the research topics of 'A BDNF-Mediated Push-Pull Plasticity Mechanism for Synaptic Clustering'. Together they form a unique fingerprint.

Cite this