
Matrix metalloproteinase-9 (MMP-9) is rapidly released from dendritic spines upon synaptic stimulation and is essential for the induction and maintenance of structural long-term potentiation (sLTP) by promoting the maturation of brain-derived neurotrophic factor (BDNF) and activation of its receptor TrkB.


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Synaptic plasticity underlies learning and memory processes as well as contributes, in its aberrant form, to neuropsychiatric disorders. One of its major forms is structural long-term potentiation (sLTP), an activity-dependent growth of dendritic spines that harbor excitatory synapses. The process depends on the release of brain-derived neurotrophic factor (BDNF), and activation of its receptor, TrkB. Matrix metalloproteinase-9 (MMP-9), an extracellular protease is essential for many forms of neuronal plasticity engaged in physiological as well as pathological processes. Here, we utilized two-photon microscopy and two-photon glutamate uncaging to demonstrate that MMP-9 activity is essential for sLTP and is rapidly (∼seconds) released from dendritic spines in response to synaptic stimulation. Moreover, we show that either chemical or genetic inhibition of MMP-9 impairs TrkB activation, as measured by fluorescence lifetime imaging microscopy of FRET sensor. Furthermore, we provide evidence for a cell-free cleavage of proBDNF into mature BDNF by MMP-9. Our findings point to the autocrine mechanism of action of MMP-9 through BDNF maturation and TrkB activation during sLTP.

### Competing Interest Statement

R.Y. is a founder of Florida Lifetime Imaging LLC.

BDNF signaling requires Matrix Metalloproteinase-9 during structural synaptic plasticity

matrix-metalloproteinase-9-rapidly-releases-and-activates-bdnf-to-control-structural-synaptic-plasticity


Matrix Metalloproteinase-9 Rapidly Releases and Activates BDNF to Control Structural Synaptic Plasticity
