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Volume 13
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10.3390/cells13191627
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

Do Perineuronal Nets Stabilize the Engram of a Synaptic Circuit?

by
Varda Lev-Ram
1,*,
Sakina Palida Lemieux
1,
Thomas J. Deerinck
2,
Eric A. Bushong
2,
Alex J. Perez
2,
Denise R. Pritchard
1,
Brandon H. Toyama
3,
Sung Kyu R. Park
4,
Daniel B. McClatchy
4,
Jeffrey N. Savas
4,5,
Michael Whitney
1,
Stephen R. Adams
1,
Mark H. Ellisman
2,6,
John Yates III
4,7 and
Roger Y. Tsien
1,8,9,†
1
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093, USA
2
National Center for Microscopy and Imaging Research, University of California, San Diego, La Jolla, CA 92093, USA
3
Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA
4
Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA
5
Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60208, USA
6
Neurosciences, University of California, San Diego, La Jolla, CA 92093, USA
7
Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA
8
Department of Chemistry & Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
9
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, CA 92093, USA
*
Author to whom correspondence should be addressed.
†
Deceased, 24 August 2016.
Cells 2024, 13(19), 1627; https://doi.org/10.3390/cells13191627
Submission received: 14 June 2024 / Revised: 4 August 2024 / Accepted: 9 August 2024 / Published: 29 September 2024
(This article belongs to the Special Issue Diving Deep into Synaptic Transmission)
Versions Notes

Abstract

Perineuronal nets (PNNs), a specialized form of extra cellular matrix (ECM), surround numerous neurons in the CNS and allow synaptic connectivity through holes in its structure. We hypothesize that PNNs serve as gatekeepers that guard and protect synaptic territory and thus may stabilize an engram circuit. We present high-resolution and 3D EM images of PNN-engulfed neurons in mice brains, showing that synapses occupy the PNN holes and that invasion of other cellular components is rare. PNN constituents in mice brains are long-lived and can be eroded faster in an enriched environment, while synaptic proteins have a high turnover rate. Preventing PNN erosion by using pharmacological inhibition of PNN-modifying proteases or matrix metalloproteases 9 (MMP9) knockout mice allowed normal fear memory acquisition but diminished long-term memory stabilization, supporting the above hypothesis.
Keywords: perineuronal nets; life-long-memory; fear conditioning; SILAM; SBEM perineuronal nets; life-long-memory; fear conditioning; SILAM; SBEM

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MDPI and ACS Style

Lev-Ram, V.; Lemieux, S.P.; Deerinck, T.J.; Bushong, E.A.; Perez, A.J.; Pritchard, D.R.; Toyama, B.H.; Park, S.K.R.; McClatchy, D.B.; Savas, J.N.; et al. Do Perineuronal Nets Stabilize the Engram of a Synaptic Circuit? Cells 2024, 13, 1627. https://doi.org/10.3390/cells13191627

AMA Style

Lev-Ram V, Lemieux SP, Deerinck TJ, Bushong EA, Perez AJ, Pritchard DR, Toyama BH, Park SKR, McClatchy DB, Savas JN, et al. Do Perineuronal Nets Stabilize the Engram of a Synaptic Circuit? Cells. 2024; 13(19):1627. https://doi.org/10.3390/cells13191627

Chicago/Turabian Style

Lev-Ram, Varda, Sakina Palida Lemieux, Thomas J. Deerinck, Eric A. Bushong, Alex J. Perez, Denise R. Pritchard, Brandon H. Toyama, Sung Kyu R. Park, Daniel B. McClatchy, Jeffrey N. Savas, and et al. 2024. "Do Perineuronal Nets Stabilize the Engram of a Synaptic Circuit?" Cells 13, no. 19: 1627. https://doi.org/10.3390/cells13191627

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