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bioRxiv · 10.1101/2023.12.08.569797

Matrix Metalloproteinase-9 controls structural synaptic plasticity via BDNF-dependent signaling

Legutko, D.·Kuzniewska, B.·Kalita, K.·Yasuda, R.·Kaczmarek, L.·Michaluk, P.
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Abstract

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.

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Legutko, D., Kuzniewska, B., Kalita, K., Yasuda, R., Kaczmarek, L., Michaluk, P.. 2023-12-09. Matrix Metalloproteinase-9 controls structural synaptic plasticity via BDNF-dependent signaling. https://doi.org/10.1101/2023.12.08.569797

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