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

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

Onderzoeksoutput: Bijdrage aan wetenschappelijk tijdschrift/periodieke uitgaveArtikelWetenschappelijkpeer review

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Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)2063-2074
Aantal pagina's12
TijdschriftCell Reports
Volume24
Nummer van het tijdschrift8
DOI's
StatusGepubliceerd - 21 aug 2018

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