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Updated: Jan 8, 2026

Preparation of Synaptoneurosomes from Mouse Cortex using a Discontinuous Percoll-Sucrose Density Gradient
Published on: September 17, 2011
Extracellular matrix proteolysis maintains synapse plasticity during brain development
Haruna Nakajo1, Ran Cao1, Supriya A Mula1
1Department of Psychiatry and Behavioral Sciences/Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
None:
The extracellular matrix (ECM) regulates synaptic plasticity via mechanisms that are still being defined and have been studied predominantly in adulthood. Here, using live imaging of excitatory synapses in zebrafish hindbrain, we observed a bimodal distribution of short-lived (dynamic) and longer-lived (stable) synapses. Disruption of ECM via digestion or brevican deletion destabilized dynamic synapses and led to decreased synapse density. Conversely, loss of matrix metalloproteinase 14 (MMP14) led to accumulation of brevican and increased the lifetime of the dynamic synapse pool without affecting the stable synapse pool, resulting in increased overall synapse density. Microglial MMP14 was essential to these effects in both fish and human induced pluripotent stem cell-derived cultures. Both MMP14 and brevican were required for experience-dependent synapse plasticity in a motor learning assay. These data, complemented by mathematical modeling, define an essential role of ECM remodeling in maintaining a dynamic subset of synapses during brain development.
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