biostudies-literatureUnknownLegutko DNIMH NIH HHSNINDS NIH HHSSynaptic 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.bioRxiv : the preprint server for biology2023.12.08.569797https://www.ebi.ac.uk/biostudies/studies/S-EPMC10723398biostudies-literatureBDNF signaling requires Matrix Metalloproteinase-9 during structural synaptic plasticity.PMC10723398R35 NS116804R01 MH080047Legutko DMichaluk PKalita KYasuda RKuzniewska BKaczmarek LfalseBDNF signaling requires Matrix Metalloproteinase-9 during structural synaptic plasticity.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.2024-01-01T00:00:00Z2024 Jan2026-06-05T03:23:35.732Z2025-04-04T10:42:28.637ZS-EPMC107233983810620910.1101/2023.12.08.569797