BDNF-driven synaptic plasticity requires autocrine matrix metalloproteinase-9 activity.

Area of Science:

• Neuroscience
• Molecular Biology
• Cellular Plasticity

Background:

• Structural plasticity of dendritic spines underlies learning and memory.
• This plasticity depends on brain-derived neurotrophic factor (BDNF) and its receptor TrkB.
• Mature BDNF requires proteolytic cleavage from its precursor, proBDNF, to bind TrkB.

Purpose of the Study:

• To investigate the role of matrix metalloproteinase-9 (MMP-9) in BDNF maturation and TrkB activation.
• To determine if MMP-9 is involved in the structural plasticity of dendritic spines.

Main Methods:

• Utilized two-photon microscopy for real-time observation.
• Employed single-spine stimulation via glutamate uncaging.
• Assessed MMP-9 release and proteolytic activity post-stimulation.
• Investigated MMP-9's direct cleavage of proBDNF.

Main Results:

• MMP-9 is rapidly released upon synaptic stimulation, with activity localized to activated spines within 2 minutes.
• MMP-9 activity is essential for tropomyosin receptor kinase B (TrkB) activation.
• MMP-9 directly cleaves pro-brain-derived neurotrophic factor (proBDNF) into mature BDNF.
• MMP-9 is required for activity-dependent structural plasticity of dendritic spines.

Conclusions:

• Matrix metalloproteinase-9 (MMP-9) plays a critical role in processing brain-derived neurotrophic factor (BDNF).
• MMP-9 directly facilitates the maturation of BDNF, enabling TrkB receptor activation.
• This MMP-9-BDNF interaction is essential for regulating dendritic spine structural plasticity, impacting learning and memory mechanisms.