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

Abstract

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.