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Do Perineuronal Nets Stabilize the Engram of a Synaptic Circuit?
Varda Lev-Ram1, Sakina Palida Lemieux1, Thomas J Deerinck2
1Department of Pharmacology, University of California San Diego, CA 92093, USA.
Cells
|October 15, 2024
Summary
Perineuronal nets (PNNs) protect neuronal circuits by guarding synapses. Inhibiting PNN erosion impairs long-term memory stabilization, suggesting PNNs are crucial for memory persistence.
Area of Science:
- Neuroscience
- Cell Biology
- Extracellular Matrix Research
Background:
- Perineuronal nets (PNNs) are specialized extracellular matrix structures ensheathing neurons in the central nervous system (CNS).
- PNNs contain unique components and are thought to play roles in synaptic plasticity and circuit stability.
- Their precise function as gatekeepers of synaptic territory remains to be fully elucidated.
Purpose of the Study:
- To investigate the role of PNNs as gatekeepers of synaptic territory.
- To determine the impact of PNN structure and dynamics on memory stabilization.
- To test the hypothesis that PNNs stabilize engram circuits.
Main Methods:
- High-resolution and 3D electron microscopy (EM) imaging of PNN-engulfed neurons in mouse brains.
- Analysis of PNN constituent longevity and turnover rates compared to synaptic proteins.
- Pharmacological inhibition of PNN-modifying proteases and utilization of matrix metalloproteinase 9 (MMP9) knockout mice.
Main Results:
- EM images confirmed synapses within PNN holes, with rare invasion by other cellular components.
- PNN constituents exhibit long-term stability, while synaptic proteins have high turnover rates.
- Inhibition of PNN erosion preserved fear memory acquisition but impaired long-term memory stabilization.
Conclusions:
- PNNs act as gatekeepers, protecting synaptic territories and stabilizing neural circuits.
- PNN integrity is essential for the long-term consolidation of memories.
- Modulating PNNs offers a potential avenue for understanding and treating memory disorders.
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