Do Perineuronal Nets Stabilize the Engram of a Synaptic Circuit?

Autor:	Lev-Ram V; Department of Pharmacology, University of California San Diego, CA 92093, USA., Lemieux SP; Department of Pharmacology, University of California San Diego, CA 92093, USA., Deerinck TJ; National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, CA 92093, USA., Bushong EA; National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, CA 92093, USA., Perez AJ; National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, CA 92093, USA., Pritchard DR; Department of Pharmacology, University of California San Diego, CA 92093, USA., Toyama BH; Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA., Park SKR; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA., McClatchy DB; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA., Savas JN; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.; Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60208, USA., Whitney M; Department of Pharmacology, University of California San Diego, CA 92093, USA., Adams SR; Department of Pharmacology, University of California San Diego, CA 92093, USA., Ellisman MH; National Center for Microscopy and Imaging Research, University of California San Diego, La Jolla, CA 92093, USA.; Neurosciences, University of California San Diego, La Jolla, CA 92093, USA., Yates J 3rd; Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.; Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037, USA., Tsien RY; Department of Pharmacology, University of California San Diego, CA 92093, USA.; Department of Chemistry & Biochemistry, University of California San Diego, La Jolla, CA 92093, USA.; Howard Hughes Medical Institute, University of California San Diego, La Jolla, CA 92093, USA.
Jazyk:	angličtina
Zdroj:	Cells [Cells] 2024 Sep 29; Vol. 13 (19). Date of Electronic Publication: 2024 Sep 29.
DOI:	10.3390/cells13191627
Abstrakt:	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.
Databáze:	MEDLINE
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