Do perineuronal nets stabilize the engram of a synaptic circuit?

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Perineuronal nets (PNNs) are extracellular matrix structures surrounding neurons in the central nervous system.
• PNNs regulate synaptic connectivity and plasticity.
• Their role in memory stabilization, particularly long-term memory, is under investigation.

Approach:

• High-resolution 3D electron microscopy visualized PNNs and associated synapses.
• Stable Isotope Labeling in Mammals (SILAM) assessed protein longevity within PNNs.
• Pharmacological and genetic methods inhibited PNN-modifying proteases and MMP9 to study memory consolidation.

Key Points:

• Synapses occupy the holes within PNNs, with rare invasion by other cellular components.
• PNN constituents are long-lived, contrasting with the high turnover rate of synaptic proteins.
• Inhibition of PNN erosion impaired remote memory stabilization while preserving initial acquisition.

Conclusions:

• PNNs may act as gatekeepers, stabilizing engram circuits and contributing to memory persistence.
• The structural integrity of PNNs is critical for the consolidation of remote memories.
• These findings support the hypothesis that PNNs play a vital role in long-term memory storage.