All components of the CNS are surrounded by a diffuse extracellular matrix (ECM) containing chondroitin sulphate proteoglycans (CSPGs), heparan sulphate proteoglycans (HSPGs), hyaluronan, various glycoproteins including tenascins and thrombospondin, and many other molecules that are secreted into the ECM and bind to ECM components. In addition, some neurons, particularly inhibitory GABAergic parvalbumin-positive (PV) interneurons, are surrounded by a more condensed cartilage-like ECM called perineuronal nets (PNNs). PNNs surround the soma and proximal dendrites as net-like structures that surround the synapses. Attention has focused on the role of PNNs in the control of plasticity, but it is now clear that PNNs also play an important part in the modulation of memory. In this review we summarize the role of the ECM, particularly the PNNs, in the control of various types of memory and their participation in memory pathology. PNNs are now being considered as a target for the treatment of impaired memory. There are many potential treatment targets in PNNs, mainly through modulation of the sulphation, binding, and production of the various CSPGs that they contain or through digestion of their sulphated glycosaminoglycans.

Centre for Reconstructive Neuroscience Institute for Experimental Medicine CAS Videnska 1083 Prague 4 Prague Czech Republic

Department of Biosciences University of Oslo Oslo Norway

John van Geest Centre for Brain Repair Department Clinical Neurosciences University of Cambridge Cambridge CB2 0PY UK

Robert S Dow Neurobiology Laboratories Legacy Research Institute Portland OR USA

School of Biomedical Sciences University of Leeds Leeds LS2 9JT UK

Zobrazit více v PubMed

Fawcett JW, Oohashi T, Pizzorusso T. The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function. Nat Rev Neurosci. 2019;20:451–65. doi: 10.1038/s41583-019-0196-3. PubMed DOI

Venstrom KA, Reichardt LF. Extracellular matrix 2: role of extracellular matrix molecules and their receptors in the nervous system. FASEB J. 1993;7:996–1003. doi: 10.1096/fasebj.7.11.8370483. PubMed DOI

Jenkins HG, Bachelard HS. Developmental and age-related changes in rat brain glycosaminoglycans. J Neurochem. 1988;51:1634–40. doi: 10.1111/j.1471-4159.1988.tb01134.x. PubMed DOI

Kadomatsu K, Sakamoto K. Sulfated glycans in network rewiring and plasticity after neuronal injuries. Neurosci Res. 2014;78:50–54. doi: 10.1016/j.neures.2013.10.005. PubMed DOI

Wang H, Katagiri Y, McCann TE, Unsworth E, Goldsmith P, Yu ZX, et al. Chondroitin-4-sulfation negatively regulates axonal guidance and growth. J cell Sci. 2008;121:3083–91. doi: 10.1242/jcs.032649. PubMed DOI PMC

Bradbury EJ, Moon LDF, Popat RJ, King VR, Bennett GS, Patel PN, et al. Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature. 2002;416:636–40. doi: 10.1038/416636a. PubMed DOI

Asher RA, Morgenstern DA, Moon LDF, Fawcett JW Chondroitin sulphate proteoglycans: inhibitory components of the glial scar. Progress in Brain Res. 2001;132:611–9. PubMed

Moon LDF, Asher RA, Rhodes KE, Fawcett JW. Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC. Nat Neurosci. 2001;4:465–6. doi: 10.1038/87415. PubMed DOI

McKeon RJ, Höke A, Silver J. Injury-induced proteoglycans inhibit the potential for laminin-mediated axon growth on astrocytic scars. Exp Neurol. 1995;136:32–43. doi: 10.1006/exnr.1995.1081. PubMed DOI

Yu P, Pearson CS, Geller HM. Flexible roles for proteoglycan sulfation and receptor signaling. Trends Neurosci. 2018;41:47–61. doi: 10.1016/j.tins.2017.10.005. PubMed DOI PMC

Mikami T, Kitagawa H. Biosynthesis and function of chondroitin sulfate. Biochim Biophys Acta. 2013;1830:4719–33. doi: 10.1016/j.bbagen.2013.06.006. PubMed DOI

Lander C, Zhang H, Hockfield S. Neurons produce a neuronal cell surface-associated chondroitin sulfate proteoglycan. J Neurosci. 1998;18:174–83. doi: 10.1523/JNEUROSCI.18-01-00174.1998. PubMed DOI PMC

Miyata S, Kitagawa H. Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan. Biochim Biophys Acta Gen Subj. 2017;1861:2420–34. doi: 10.1016/j.bbagen.2017.06.010. PubMed DOI

Yamaguchi Y. Lecticans: organizers of the brain extracellular matrix. Cell Mol Life Sci CMLS. 2000;57:276–89. doi: 10.1007/PL00000690. PubMed DOI PMC

Kwok JCF, Carulli D, Fawcett JW. In vitro modeling of perineuronal nets: hyaluronan synthase and link protein are necessary for their formation and integrity. J Neurochem. 2010;114:1447–59. PubMed

Stevens SR, Longley CM, Ogawa Y, Teliska LH, Arumanayagam AS, Nair S, et al. Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K(+) channels. Elife. 2021;10:e66491. doi: 10.7554/eLife.66491. PubMed DOI PMC

Eill GJ, Sinha A, Morawski M, Viapiano MS, Matthews RT. The protein tyrosine phosphatase RPTPzeta/phosphacan is critical for perineuronal net structure. J Biol Chem. 2020;295:955–68. doi: 10.1016/S0021-9258(17)49907-8. PubMed DOI PMC

Giamanco KA, Matthews RT. Deconstructing the perineuronal net: cellular contributions and molecular composition of the neuronal extracellular matrix. Neuroscience. 2012;218:367–84. doi: 10.1016/j.neuroscience.2012.05.055. PubMed DOI PMC

Aspberg A, Miura R, Bourdoulous S, Shimonaka M, Heinegård D, Schachner M, et al. The C-type lectin domains of lecticans, a family of aggregating chondroitin sulfate proteoglycans, bind tenascin-R by protein– protein interactions independent of carbohydrate moiety. Proc Natl Acad Sci USA. 1997;94:10116–21. doi: 10.1073/pnas.94.19.10116. PubMed DOI PMC

Morawski M, Dityatev A, Hartlage-Rübsamen M, Blosa M, Holzer M, Flach K, et al. Tenascin-R promotes assembly of the extracellular matrix of perineuronal nets via clustering of aggrecan. Philos Trans R Soc Lond B: Biol Sci. 2014;369:20140046. doi: 10.1098/rstb.2014.0046. PubMed DOI PMC

Oohashi T, Edamatsu M, Bekku Y, Carulli D. The hyaluronan and proteoglycan link proteins: Organizers of the brain extracellular matrix and key molecules for neuronal function and plasticity. Exp Neurol. 2015;274:134–44. doi: 10.1016/j.expneurol.2015.09.010. PubMed DOI

Arranz AM, Perkins KL, Irie F, Lewis DP, Hrabe J, Xiao F, et al. Hyaluronan deficiency due to Has3 knock-out causes altered neuronal activity and seizures via reduction in brain extracellular space. J Neurosci. 2014;34:6164–76. doi: 10.1523/JNEUROSCI.3458-13.2014. PubMed DOI PMC

Beurdeley M, Spatazza J, Lee HH, Sugiyama S, Bernard C, Di Nardo AA, et al. Otx2 binding to perineuronal nets persistently regulates plasticity in the mature visual cortex. J Neurosci. 2012;32:9429–37. doi: 10.1523/JNEUROSCI.0394-12.2012. PubMed DOI PMC

Chang MC, Park JM, Pelkey KA, Grabenstatter HL, Xu D, Linden DJ, et al. Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons. Nat Neurosci. 2010;13:1090–7. doi: 10.1038/nn.2621. PubMed DOI PMC

De Wit J, De Winter F, Klooster J, Verhaagen J. Semaphorin 3A displays a punctate distribution on the surface of neuronal cells and interacts with proteoglycans in the extracellular matrix. Mol Cell Neurosci. 2005;29:40–55. doi: 10.1016/j.mcn.2004.12.009. PubMed DOI

Spatazza J, Lee HH, Di Nardo AA, Tibaldi L, Joliot A, Hensch TK, et al. Choroid-plexus-derived Otx2 homeoprotein constrains adult cortical plasticity. Cell Rep. 2013;3:1815–23. doi: 10.1016/j.celrep.2013.05.014. PubMed DOI PMC

Vo T, Carulli D, Ehlert EME, Kwok JCF, Dick G, Mecollari V, et al. The chemorepulsive axon guidance protein semaphorin3A is a constituent of perineuronal nets in the adult rodent brain. Mol Cell Neurosci. 2013;56:186–200. doi: 10.1016/j.mcn.2013.04.009. PubMed DOI

Dick G, Tan CL, Alves JN, Ehlert EM, Miller GM, Hsieh-Wilson LC, et al. Semaphorin 3A binds to the perineuronal nets via chondroitin sulfate type E motifs in rodent brains. J Biol Chem. 2013;288:27384–95. doi: 10.1074/jbc.M111.310029. PubMed DOI PMC

Van’t Spijker HM, Rowlands D, Rossier J, Haenzi B, Fawcett JW, Kwok JCF. Neuronal Pentraxin 2 Binds PNNs and Enhances PNN Formation. Neural Plasticity. 2019;2019:6804575. doi: 10.1155/2019/6804575. PubMed DOI PMC

Boggio EM, Ehlert EM, Lupori L, Moloney EB, De Winter F, Vander, et al. Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex. Mol Neurobiol. 2019;56:5987–97. doi: 10.1007/s12035-019-1499-0. PubMed DOI

Carulli D, Broersen R, de Winter F, Muir EM, Meskovic M, de Waal M, et al. Cerebellar plasticity and associative memories are controlled by perineuronal nets. Proc Natl Acad Sci USA. 2020;117:6855–65. doi: 10.1073/pnas.1916163117. PubMed DOI PMC

Djerbal L, Vivès RR, Lopin-Bon C, Richter RP, Kwok JCF, Lortat-Jacob H Semaphorin 3A binding to chondroitin sulfate E enhances the biological activity of the protein, and cross-links and rigidifies glycosaminoglycan matrices. bioRxiv 2019; bioRxiv 851121; 10.1101/851121

Lang BT, Cregg JM, DePaul MA, Tran AP, Xu K, Dyck SM, et al. Modulation of the proteoglycan receptor PTPsigma promotes recovery after spinal cord injury. Nature. 2015;518:404–8. doi: 10.1038/nature13974. PubMed DOI PMC

Favuzzi E, Marques-Smith A, Deogracias R, Winterflood CM, Sanchez-Aguilera A, Mantoan L, et al. Activity-Dependent Gating of Parvalbumin Interneuron Function by the Perineuronal Net Protein Brevican. Neuron. 2017;95:639–55 e610. doi: 10.1016/j.neuron.2017.06.028. PubMed DOI

Frischknecht R, Heine M, Perrais D, Seidenbecher CI, Choquet D, Gundelfinger ED. Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity. Nat Neurosci. 2009;12:897–904. doi: 10.1038/nn.2338. PubMed DOI

Ethell IM, Ethell DW. Matrix metalloproteinases in brain development and remodeling: synaptic functions and targets. J Neurosci Res. 2007;85:2813–23. doi: 10.1002/jnr.21273. PubMed DOI

Beroun A, Mitra S, Michaluk P, Pijet B, Stefaniuk M, Kaczmarek L. MMPs in learning and memory and neuropsychiatric disorders. Cell Mol Life Sci. 2019;76:3207–28. doi: 10.1007/s00018-019-03180-8. PubMed DOI PMC

Mitlohner J, Kaushik R, Niekisch H, Blondiaux A, Gee CE, Happel MFK, et al. Dopamine Receptor Activation Modulates the Integrity of the Perisynaptic Extracellular Matrix at Excitatory Synapses. Cells. 2020;9:260. doi: 10.3390/cells9020260. PubMed DOI PMC

Nguyen PT, Dorman LC, Pan S, Vainchtein ID, Han RT, Nakao-Inoue H, et al. Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity. Cell. 2020;182:388–403. doi: 10.1016/j.cell.2020.05.050. PubMed DOI PMC

Orlando C, Ster J, Gerber U, Fawcett JW, Raineteau O. Peridendritic chondroitin sulfate proteoglycans restrict structural plasticity in an integrin-dependent manner. J Neurosci. 2012;32:18009–17. doi: 10.1523/JNEUROSCI.2406-12.2012. PubMed DOI PMC

de Vivo L, Landi S, Panniello M, Baroncelli L, Chierzi S, Mariotti L, et al. Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex. Nat Commun. 2013;4:1484. doi: 10.1038/ncomms2491. PubMed DOI

Oray S, Majewska A, Sur M. Dendritic spine dynamics are regulated by monocular deprivation and extracellular matrix degradation. Neuron. 2004;44:1021–30. doi: 10.1016/j.neuron.2004.12.001. PubMed DOI

Donato F, Rompani SB, Caroni P. Parvalbumin-expressing basket-cell network plasticity induced by experience regulates adult learning. Nature. 2013;504:272–6. doi: 10.1038/nature12866. PubMed DOI

Ruzicka J, Dalecka M, Safrankova K, Peretti D, Mallucci G, Jendelova P et al. Perineuronal nets affect memory and learning after synapse withdrawal. bioRxiv 2021.04.13.439599; 10.1101/2021.04.13.439599. PubMed PMC

Yang S, Gigout S, Molinaro A, Naito-Matsui Y, Hilton S, Foscarin S et al. Chondroitin 6-sulphate is required for neuroplasticity and memory in ageing. Mol Psychiatry 2021;26:5658–68. PubMed PMC

Christensen AC, Lensjo KK, Lepperod ME, Dragly SA, Sutterud H, Blackstad JS, et al. Perineuronal nets stabilize the grid cell network. Nat Commun. 2021;12:253. doi: 10.1038/s41467-020-20241-w. PubMed DOI PMC

Lensjo KK, Lepperod ME, Dick G, Hafting T, Fyhn M. Removal of Perineuronal Nets Unlocks Juvenile Plasticity Through Network Mechanisms of Decreased Inhibition and Increased Gamma Activity. J Neurosci. 2017;37:1269–83. doi: 10.1523/JNEUROSCI.2504-16.2016. PubMed DOI PMC

Corvetti L, Rossi F. Degradation of chondroitin sulfate proteoglycans induces sprouting of intact purkinje axons in the cerebellum of the adult rat. J Neurosci. 2005;25:7150–8. doi: 10.1523/JNEUROSCI.0683-05.2005. PubMed DOI PMC

Sullivan CS, Gotthard I, Wyatt EV, Bongu S, Mohan V, Weinberg RJ, et al. Perineuronal Net Protein Neurocan Inhibits NCAM/EphA3 Repellent Signaling in GABAergic Interneurons. Sci Rep. 2018;8:6143. doi: 10.1038/s41598-018-24272-8. PubMed DOI PMC

Choquet D, Opazo P. The role of AMPAR lateral diffusion in memory. Semin Cell Dev Biol. 2022;125:76–83. doi: 10.1016/j.semcdb.2022.01.009. PubMed DOI

Schweitzer B, Singh J, Fejtova A, Groc L, Heine M, Frischknecht R. Hyaluronic acid based extracellular matrix regulates surface expression of GluN2B containing NMDA receptors. Sci Rep. 2017;7:10991. doi: 10.1038/s41598-017-07003-3. PubMed DOI PMC

Edamatsu M, Miyano R, Fujikawa A, Fujii F, Hori T, Sakaba T, et al. Hapln4/Bral2 is a selective regulator for formation and transmission of GABAergic synapses between Purkinje and deep cerebellar nuclei neurons. J Neurochem. 2018;14:748–63. doi: 10.1111/jnc.14571. PubMed DOI

Romberg C, Yang S, Melani R, Andrews MR, Horner AE, Spillantini MG, et al. Depletion of Perineuronal Nets Enhances Recognition Memory and Long-Term Depression in the Perirhinal Cortex. J Neurosci. 2013;33:7057–65. doi: 10.1523/JNEUROSCI.6267-11.2013. PubMed DOI PMC

Heikkinen A, Pihlajaniemi T, Faissner A, Yuzaki M. Neural ECM and synaptogenesis. Prog Brain Res. 2014;214:29–51. doi: 10.1016/B978-0-444-63486-3.00002-5. PubMed DOI

Simonetti M, Paldy E, Njoo C, Bali KK, Worzfeld T, Pitzer C, et al. The impact of Semaphorin 4C/Plexin-B2 signaling on fear memory via remodeling of neuronal and synaptic morphology. Mol Psychiatry. 2021;26:1376–98. doi: 10.1038/s41380-019-0491-4. PubMed DOI PMC

Carulli D, de Winter F, Verhaagen J. Semaphorins in Adult Nervous System Plasticity and Disease. Front Synaptic Neurosci. 2021;13:672891. doi: 10.3389/fnsyn.2021.672891. PubMed DOI PMC

Apostolova I, Irintchev A, Schachner M. Tenascin-R restricts posttraumatic remodeling of motoneuron innervation and functional recovery after spinal cord injury in adult mice. J Neurosci. 2006;26:7849–59. doi: 10.1523/JNEUROSCI.1526-06.2006. PubMed DOI PMC

Wiera G, Mozrzymas JW. Extracellular Metalloproteinases in the Plasticity of Excitatory and Inhibitory Synapses. Cells. 2021;10:2055. doi: 10.3390/cells10082055. PubMed DOI PMC

Wingert JC, Sorg BA. Impact of Perineuronal Nets on Electrophysiology of Parvalbumin Interneurons, Principal Neurons, and Brain Oscillations: A Review. Front Synaptic Neurosci. 2021;13:673210. doi: 10.3389/fnsyn.2021.673210. PubMed DOI PMC

Bukalo O, Schachner M, Dityatev A. Modification of extracellular matrix by enzymatic removal of chondroitin sulfate and by lack of tenascin-R differentially affects several forms of synaptic plasticity in the hippocampus. Neuroscience. 2001;104:359–69. doi: 10.1016/S0306-4522(01)00082-3. PubMed DOI

Kochlamazashvili G, Henneberger C, Bukalo O, Dvoretskova E, Senkov O, Lievens PM, et al. The extracellular matrix molecule hyaluronic acid regulates hippocampal synaptic plasticity by modulating postsynaptic L-type Ca(2+) channels. Neuron. 2010;67:116–28. doi: 10.1016/j.neuron.2010.05.030. PubMed DOI PMC

Shi W, Wei X, Wang X, Du S, Liu W, Song J, et al. Perineuronal nets protect long-term memory by limiting activity-dependent inhibition from parvalbumin interneurons. Proc Natl Acad Sci USA 2019;116:27063–73. PubMed PMC

Saghatelyan AK, Dityatev A, Schmidt S, Schuster T, Bartsch U, Schachner M. Reduced perisomatic inhibition, increased excitatory transmission, and impaired long-term potentiation in mice deficient for the extracellular matrix glycoprotein tenascin-R. Mol Cell Neurosci. 2001;17:226–40. doi: 10.1006/mcne.2000.0922. PubMed DOI

Zhou XH, Brakebusch C, Matthies H, Oohashi T, Hirsch E, Moser M, et al. Neurocan is dispensable for brain development. Mol Cell Biol. 2001;21:5970–8. doi: 10.1128/MCB.21.17.5970-5978.2001. PubMed DOI PMC

Brakebusch C, Seidenbecher CI, Asztely F, Rauch U, Matthies H, Meyer H, et al. Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory. Mol Cell Biol. 2002;22:7417–27. doi: 10.1128/MCB.22.21.7417-7427.2002. PubMed DOI PMC

Carstens KE, Phillips ML, Pozzo-Miller L, Weinberg RJ, Dudek SM. Perineuronal Nets Suppress Plasticity of Excitatory Synapses on CA2 Pyramidal Neurons. J Neurosci. 2016;36:6312–20. doi: 10.1523/JNEUROSCI.0245-16.2016. PubMed DOI PMC

Khoo GH, Lin YT, Tsai TC, Hsu KS. Perineuronal Nets Restrict the Induction of Long-Term Depression in the Mouse Hippocampal CA1 Region. Mol Neurobiol. 2019;56:6436–50. doi: 10.1007/s12035-019-1526-1. PubMed DOI

Gottschling C, Wegrzyn D, Denecke B, Faissner A. Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses. Sci Rep. 2019;9:13939. doi: 10.1038/s41598-019-50404-9. PubMed DOI PMC

Rowlands D, Lensjo KK, Dinh T, Yang S, Andrews MR, Hafting T, et al. Aggrecan directs extracellular matrix-mediateD NEURONAL Plasticity. J Neurosci. 2018;38:10102–13. doi: 10.1523/JNEUROSCI.1122-18.2018. PubMed DOI PMC

Hirono M, Watanabe S, Karube F, Fujiyama F, Kawahara S, Nagao S, et al. Perineuronal nets in the deep cerebellar nuclei regulate gabaergic transmission and delay eyeblink conditioning. J Neurosci. 2018;38:6130–44. doi: 10.1523/JNEUROSCI.3238-17.2018. PubMed DOI PMC

Lensjo KK, Christensen AC, Tennoe S, Fyhn M, Hafting T Differential Expression and Cell-Type Specificity of Perineuronal Nets in Hippocampus, Medial Entorhinal Cortex, and Visual Cortex Examined in the Rat and Mouse. eNeuro 2017;4:0379–0316. PubMed PMC

Blosa M, Sonntag M, Jager C, Weigel S, Seeger J, Frischknecht R, et al. The extracellular matrix molecule brevican is an integral component of the machinery mediating fast synaptic transmission at the calyx of Held. J Physiol. 2015;593:4341–60. doi: 10.1113/JP270849. PubMed DOI PMC

Nikonenko A, Schmidt S, Skibo G, Bruckner G, Schachner M. Tenascin-R-deficient mice show structural alterations of symmetric perisomatic synapses in the CA1 region of the hippocampus. J Comp Neurol. 2003;456:338–49. doi: 10.1002/cne.10537. PubMed DOI

Evers MR, Salmen B, Bukalo O, Rollenhagen A, Bosl MR, Morellini F, et al. Impairment of L-type Ca2+ channel-dependent forms of hippocampal synaptic plasticity in mice deficient in the extracellular matrix glycoprotein tenascin-C. J Neurosci. 2002;22:7177–94. doi: 10.1523/JNEUROSCI.22-16-07177.2002. PubMed DOI PMC

Carulli D, Verhaagen J An Extracellular Perspective on CNS Maturation: Perineuronal Nets and the Control of Plasticity. Int J Mol Sci 2021;22:2434 PubMed PMC

Freeman JH, Steinmetz AB. Neural circuitry and plasticity mechanisms underlying delay eyeblink conditioning. Learn Mem. 2011;18:666–77. doi: 10.1101/lm.2023011. PubMed DOI PMC

Carulli D, Rhodes KE, Brown DJ, Bonnert TP, Pollack SJ, Oliver K, et al. Composition of perineuronal nets in the adult rat cerebellum and the cellular origin of their components. J Comp Neurol. 2006;494:559–77. doi: 10.1002/cne.20822. PubMed DOI

O’Dell DE, Schreurs BG, Smith-Bell C, Wang D. Disruption of rat deep cerebellar perineuronal net alters eyeblink conditioning and neuronal electrophysiology. Neurobiol Learn Mem. 2021;177:107358. doi: 10.1016/j.nlm.2020.107358. PubMed DOI PMC

American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th edn, APA, Arlington VA; 2013.

LeDoux JE, Pine DS. Using neuroscience to help understand fear and anxiety: a two-system framework. Am J Psychiatry. 2016;173:1083–93. doi: 10.1176/appi.ajp.2016.16030353. PubMed DOI

Maeng LY, Milad MR. Post-traumatic stress disorder: the relationship between the fear response and chronic stress. Chronic Stress. 2017;1:2470547017713297. doi: 10.1177/2470547017713297. PubMed DOI PMC

Gogolla N, Caroni P, Luthi A, Herry C. Perineuronal nets protect fear memories from erasure. Science. 2009;325:1258–61. doi: 10.1126/science.1174146. PubMed DOI

Hylin MJ, Orsi SA, Moore AN, Dash PK. Disruption of the perineuronal net in the hippocampus or medial prefrontal cortex impairs fear conditioning. Learn Mem. 2013;20:267–73. doi: 10.1101/lm.030197.112. PubMed DOI PMC

Banerjee SB, Gutzeit VA, Baman J, Aoued HS, Doshi NK, Liu RC, et al. Perineuronal Nets in the Adult Sensory Cortex Are Necessary for Fear Learning. Neuron. 2017;95:169–79. doi: 10.1016/j.neuron.2017.06.007. PubMed DOI PMC

Gunduz-Cinar O, Brockway E, Lederle L, Wilcox T, Halladay LR, Ding Y, et al. Identification of a novel gene regulating amygdala-mediated fear extinction. Mol Psychiatry. 2019;24:601–12. doi: 10.1038/s41380-017-0003-3. PubMed DOI PMC

Morikawa S, Ikegaya Y, Narita M, Tamura H. Activation of perineuronal net-expressing excitatory neurons during associative memory encoding and retrieval. Sci Rep. 2017;7:46024. doi: 10.1038/srep46024. PubMed DOI PMC

Lesnikova A, Casarotto PC, Fred SM, Voipio M, Winkel F, Steinzeig A, et al. Chondroitinase and antidepressants promote plasticity by releasing trkb from dephosphorylating control of ptpsigma in parvalbumin neurons. J Neurosci. 2021;41:972–80. doi: 10.1523/JNEUROSCI.2228-20.2020. PubMed DOI PMC

Lesnikova A, Casarotto P, Moliner R, Fred SM, Biojone C, Castren E. Perineuronal net receptor PTPsigma regulates retention of memories. Front Synaptic Neurosci. 2021;13:672475. doi: 10.3389/fnsyn.2021.672475. PubMed DOI PMC

Engel AK, Fries P, Singer W. Dynamic predictions: oscillations and synchrony in top-down processing. Nat Rev Neurosci. 2001;2:704–16. doi: 10.1038/35094565. PubMed DOI

Uhlhaas PJ, Roux F, Rodriguez E, Rotarska-Jagiela A, Singer W. Neural synchrony and the development of cortical networks. Trends Cogn Sci. 2010;14:72–80. doi: 10.1016/j.tics.2009.12.002. PubMed DOI

Buzsaki G, Wang XJ. Mechanisms of gamma oscillations. Annu Rev Neurosci. 2012;35:203–25. doi: 10.1146/annurev-neuro-062111-150444. PubMed DOI PMC

Stark E, Eichler R, Roux L, Fujisawa S, Rotstein HG, Buzsaki G. Inhibition-induced theta resonance in cortical circuits. Neuron. 2013;80:1263–76. doi: 10.1016/j.neuron.2013.09.033. PubMed DOI PMC

Sacco T, Sacchetti B. Role of secondary sensory cortices in emotional memory storage and retrieval in rats. Science. 2010;329:649–56. doi: 10.1126/science.1183165. PubMed DOI

Thompson EH, Lensjo KK, Wigestrand MB, Malthe-Sorenssen A, Hafting T, Fyhn M. Removal of perineuronal nets disrupts recall of a remote fear memory. Proc Natl Acad Sci USA. 2018;115:607–12. doi: 10.1073/pnas.1713530115. PubMed DOI PMC

Yang S, Cacquevel M, Saksida LM, Bussey TJ, Schneider BL, Aebischer P, et al. Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology. Exp Neurol. 2015;265:48–58. doi: 10.1016/j.expneurol.2014.11.013. PubMed DOI PMC

Yang S, Hilton S, Alves JN, Saksida LM, Bussey T, Matthews RT, et al. Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration. Neurobiol Aging. 2017;59:197–209. doi: 10.1016/j.neurobiolaging.2017.08.002. PubMed DOI

Aggleton JP, Brown MW, Albasser MM. Contrasting brain activity patterns for item recognition memory and associative recognition memory: insights from immediate-early gene functional imaging. Neuropsychologia. 2012;50:3141–55. doi: 10.1016/j.neuropsychologia.2012.05.018. PubMed DOI

Cinalli DA, Cohen SJ, Guthrie K, Stackman RW. Object recognition memory: distinct yet complementary roles of the mouse CA1 and perirhinal cortex. Front Mol Neurosci. 2020;13:527543. doi: 10.3389/fnmol.2020.527543. PubMed DOI PMC

Aggleton JP, Nelson AJD. Distributed interactive brain circuits for object-in-place memory: a place for time? Brain Neurosci Adv. 2020;4:2398212820933471. doi: 10.1177/2398212820933471. PubMed DOI PMC

Tanimizu T, Kono K, Kida S. Brain networks activated to form object recognition memory. Brain Res Bull. 2018;141:27–34. doi: 10.1016/j.brainresbull.2017.05.017. PubMed DOI

Lensjø KK, Christensen AC, Tennøe S, Fyhn M, Hafting T. Differential Expression and Cell-Type Specificity of Perineuronal Nets in Hippocampus, Medial Entorhinal Cortex, and Visual Cortex Examined in the Rat and Mouse. eNeuro 2017;4. 10.1523/ENEURO.0379-16.2017. PubMed PMC

Carstens KE, Lustberg DJ, Shaughnessy EK, McCann KE, Alexander GM, Dudek SM. Perineuronal net degradation rescues CA2 plasticity in a mouse model of Rett syndrome. J Clin Invest. 2021;131:e137221. PubMed PMC

O’Keefe J, Dostrovsky J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 1971;34:171–5. doi: 10.1016/0006-8993(71)90358-1. PubMed DOI

Fyhn M, Molden S, Witter MP, Moser EI, Moser MB. Spatial representation in the entorhinal cortex. Science. 2004;305:1258–64. doi: 10.1126/science.1099901. PubMed DOI

Hafting T, Fyhn M, Molden S, Moser MB, Moser EI. Microstructure of a spatial map in the entorhinal cortex. Nature. 2005;436:801–6. doi: 10.1038/nature03721. PubMed DOI

Hoydal OA, Skytoen ER, Andersson SO, Moser MB, Moser EI. Object-vector coding in the medial entorhinal cortex. Nature. 2019;568:400–4. doi: 10.1038/s41586-019-1077-7. PubMed DOI

Kropff E, Carmichael JE, Moser MB, Moser EI. Speed cells in the medial entorhinal cortex. Nature. 2015;523:419–24. doi: 10.1038/nature14622. PubMed DOI

Avigan PD, Cammack K, Shapiro ML. Flexible spatial learning requires both the dorsal and ventral hippocampus and their functional interactions with the prefrontal cortex. Hippocampus. 2020;30:733–44. doi: 10.1002/hipo.23198. PubMed DOI PMC

Poitreau J, Buttet M, Manrique C, Poucet B, Sargolini F, Save E. Navigation using global or local reference frames in rats with medial and lateral entorhinal cortex lesions. Behav Brain Res. 2021;413:113448. doi: 10.1016/j.bbr.2021.113448. PubMed DOI

Bertocchi I, Mele P, Ferrero G, Oberto A, Carulli D, Eva C. NPY-Y1 receptor signaling controls spatial learning and perineuronal net expression. Neuropharmacology. 2021;184:108425. doi: 10.1016/j.neuropharm.2020.108425. PubMed DOI

Yoshino Y, Shimazawa M, Nakamura S, Inoue S, Yoshida H, Shimoda M, et al. Targeted deletion of HYBID (hyaluronan binding protein involved in hyaluronan depolymerization/ KIAA1199/CEMIP) decreases dendritic spine density in the dentate gyrus through hyaluronan accumulation. Biochem Biophys Res Commun. 2018;503:1934–40. doi: 10.1016/j.bbrc.2018.07.138. PubMed DOI

Riga D, Kramvis I, Koskinen MK, van Bokhoven P, van der Harst JE, Heistek TS, et al. Hippocampal extracellular matrix alterations contribute to cognitive impairment associated with a chronic depressive-like state in rats. Sci Transl Med. 2017;9:8753. doi: 10.1126/scitranslmed.aai8753. PubMed DOI

Morellini F, Sivukhina E, Stoenica L, Oulianova E, Bukalo O, Jakovcevski I, et al. Improved reversal learning and working memory and enhanced reactivity to novelty in mice with enhanced GABAergic innervation in the dentate gyrus. Cereb Cortex. 2010;20:2712–27. doi: 10.1093/cercor/bhq017. PubMed DOI

Chao OY, de Souza Silva MA, Yang YM, Huston JP. The medial prefrontal cortex - hippocampus circuit that integrates information of object, place and time to construct episodic memory in rodents: Behavioral, anatomical and neurochemical properties. Neurosci Biobehav Rev. 2020;113:373–407. doi: 10.1016/j.neubiorev.2020.04.007. PubMed DOI PMC

Savalli G, Bashir ZI, Warburton EC. Regionally selective requirement for D1/D5 dopaminergic neurotransmission in the medial prefrontal cortex in object-in-place associative recognition memory. Learn Mem. 2015;22:69–73. doi: 10.1101/lm.036921.114. PubMed DOI PMC

Porter JT, Sepulveda-Orengo MT. Learning-induced intrinsic and synaptic plasticity in the rodent medial prefrontal cortex. Neurobiol Learn Mem. 2020;169:107117. doi: 10.1016/j.nlm.2019.107117. PubMed DOI PMC

Slaker M, Churchill L, Todd RP, Blacktop JM, Zuloaga DG, Raber J, et al. Removal of perineuronal nets in the medial prefrontal cortex impairs the acquisition and reconsolidation of a cocaine-induced conditioned place preference memory. J Neurosci. 2015;35:4190–202. doi: 10.1523/JNEUROSCI.3592-14.2015. PubMed DOI PMC

Talpos JC, Winters BD, Dias R, Saksida LM, Bussey TJ. A novel touchscreen-automated paired-associate learning (PAL) task sensitive to pharmacological manipulation of the hippocampus: a translational rodent model of cognitive impairments in neurodegenerative disease. Psychopharmacol. 2009;205:157–68. doi: 10.1007/s00213-009-1526-3. PubMed DOI

Anderson MD, Paylor JW, Scott GA, Greba Q, Winship IR, Howland JG. ChABC infusions into medial prefrontal cortex, but not posterior parietal cortex, improve the performance of rats tested on a novel, challenging delay in the touchscreen TUNL task. Learn Mem. 2020;27:222–35. doi: 10.1101/lm.050245.119. PubMed DOI PMC

Choleris E, Clipperton-Allen AE, Phan A, Kavaliers M. Neuroendocrinology of social information processing in rats and mice. Front Neuroendocrinol. 2009;30:442–59. doi: 10.1016/j.yfrne.2009.05.003. PubMed DOI

Engelmann M, Hädicke J, Noack J. Testing declarative memory in laboratory rats and mice using the nonconditioned social discrimination procedure. Nat Protoc. 2011;6:1152–62. doi: 10.1038/nprot.2011.353. PubMed DOI

Silverman JL, Yang M, Lord C, Crawley JN. Behavioural phenotyping assays for mouse models of autism. Nat Rev Neurosci. 2010;11:490–502. doi: 10.1038/nrn2851. PubMed DOI PMC

Tanimizu T, Kenney JW, Okano E, Kadoma K, Frankland PW, Kida S. Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory. J Neurosci. 2017;37:4103–16. doi: 10.1523/JNEUROSCI.3451-16.2017. PubMed DOI PMC

Reichelt AC, Gibson GD, Abbott KN, Hare DJ. A high-fat high-sugar diet in adolescent rats impairs social memory and alters chemical markers characteristic of atypical neuroplasticity and parvalbumin interneuron depletion in the medial prefrontal cortex. Food Funct. 2019;10:1985–98. doi: 10.1039/C8FO02118J. PubMed DOI

Hitti FL, Siegelbaum SA. The hippocampal CA2 region is essential for social memory. Nature. 2014;508:88–92. doi: 10.1038/nature13028. PubMed DOI PMC

Meira T, Leroy F, Buss EW, Oliva A, Park J, Siegelbaum SA. A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics. Nat Commun. 2018;9:4163. doi: 10.1038/s41467-018-06501-w. PubMed DOI PMC

Oliva A, Fernández-Ruiz A, Leroy F, Siegelbaum SA. Hippocampal CA2 sharp-wave ripples reactivate and promote social memory. Nature. 2020;587:264–9. doi: 10.1038/s41586-020-2758-y. PubMed DOI PMC

Stevenson EL, Caldwell HK. Lesions to the CA2 region of the hippocampus impair social memory in mice. Eur J Neurosci. 2014;40:3294–301. doi: 10.1111/ejn.12689. PubMed DOI PMC

Leroy F, Park J, Asok A, Brann DH, Meira T, Boyle LM, et al. A circuit from hippocampal CA2 to lateral septum disinhibits social aggression. Nature. 2018;564:213–8. doi: 10.1038/s41586-018-0772-0. PubMed DOI PMC

McDonald AJ, Hamilton PG, Barnstable CJ. Perineuronal nets labeled by monoclonal antibody VC1.1 ensheath interneurons expressing parvalbumin and calbindin in the rat amygdala. Brain Struct Funct. 2018;223:1133–48. doi: 10.1007/s00429-017-1542-8. PubMed DOI PMC

Steullet P, Cabungcal JH, Cuenod M, Do KQ. Fast oscillatory activity in the anterior cingulate cortex: dopaminergic modulation and effect of perineuronal net loss. Front Cell Neurosci. 2014;8:244. doi: 10.3389/fncel.2014.00244. PubMed DOI PMC

Cope EC, Zych AD, Katchur NJ, Waters RC, Laham BJ, Diethorn EJ, et al. Atypical perineuronal nets in the CA2 region interfere with social memory in a mouse model of social dysfunction. Mol Psychiatry 2021. 10.1038/s41380-021-01174-2. PubMed PMC

Dominguez S, Rey CC, Therreau L, Fanton A, Massotte D, Verret L, et al. Maturation of PNN and ErbB4 Signaling in Area CA2 during Adolescence Underlies the Emergence of PV Interneuron Plasticity and Social Memory. Cell Rep. 2019;29:1099–112. doi: 10.1016/j.celrep.2019.09.044. PubMed DOI

Tatsukawa T, Ogiwara I, Mazaki E, Shimohata A, Yamakawa K. Impairments in social novelty recognition and spatial memory in mice with conditional deletion of Scn1a in parvalbumin-expressing cells. Neurobiol Dis. 2018;112:24–34. doi: 10.1016/j.nbd.2018.01.009. PubMed DOI

Lee HHC, Bernard C, Ye Z, Acampora D, Simeone A, Prochiantz A, et al. Genetic Otx2 mis-localization delays critical period plasticity across brain regions. Mol Psychiatry. 2017;22:785. doi: 10.1038/mp.2017.83. PubMed DOI

Reinhard SM, Abundez-Toledo M, Espinoza K, Razak KA. Effects of developmental noise exposure on inhibitory cell densities and perineuronal nets in A1 and AAF of mice. Hear Res. 2019;381:107781. doi: 10.1016/j.heares.2019.107781. PubMed DOI

Myers AK, Ray J, Kulesza RJ., Jr Neonatal conductive hearing loss disrupts the development of the Cat-315 epitope on perineuronal nets in the rat superior olivary complex. Brain Res. 2012;1465:34–47. doi: 10.1016/j.brainres.2012.05.024. PubMed DOI

Sharma A, Dorman MF, Spahr AJ. A sensitive period for the development of the central auditory system in children with cochlear implants: implications for age of implantation. Ear Hear. 2002;23:532–9. doi: 10.1097/00003446-200212000-00004. PubMed DOI

Balmer TS, Carels VM, Frisch JL, Nick TA. Modulation of perineuronal nets and parvalbumin with developmental song learning. J Neurosci. 2009;29:12878–85. doi: 10.1523/JNEUROSCI.2974-09.2009. PubMed DOI PMC

Happel MF, Niekisch H, Castiblanco Rivera LL, Ohl FW, Deliano M, Frischknecht R. Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex. Proc Natl Acad Sci USA. 2014;111:2800–5. doi: 10.1073/pnas.1310272111. PubMed DOI PMC

Niekisch H, Steinhardt J, Berghauser J, Bertazzoni S, Kaschinski E, Kasper J, et al. Learning Induces Transient Upregulation of Brevican in the Auditory Cortex during Consolidation of Long-Term Memories. J Neurosci. 2019;39:7049–60. doi: 10.1523/JNEUROSCI.2499-18.2019. PubMed DOI PMC

Saroja SR, Sase A, Kircher SG, Wan J, Berger J, Höger H, et al. Hippocampal proteoglycans brevican and versican are linked to spatial memory of Sprague-Dawley rats in the morris water maze. J Neurochem. 2014;130:797–804. doi: 10.1111/jnc.12783. PubMed DOI

Bijata M, Labus J, Guseva D, Stawarski M, Butzlaff M, Dzwonek J, et al. Synaptic Remodeling Depends on Signaling between Serotonin Receptors and the Extracellular Matrix. Cell Rep. 2017;19:1767–82. doi: 10.1016/j.celrep.2017.05.023. PubMed DOI

Dankovich TM, Kaushik R, Olsthoorn LHM, Petersen GC, Giro PE, Kluever V, et al. Extracellular matrix remodeling through endocytosis and resurfacing of Tenascin-R. Nat Commun. 2021;12:7129. doi: 10.1038/s41467-021-27462-7. PubMed DOI PMC

Spijker S, Koskinen MK, Riga D. Incubation of depression: ECM assembly and parvalbumin interneurons after stress. Neurosci Biobehav Rev. 2020;118:65–79. doi: 10.1016/j.neubiorev.2020.07.015. PubMed DOI

Ueno H, Suemitsu S, Murakami S, Kitamura N, Wani K, Matsumoto Y, et al. Juvenile stress induces behavioral change and affects perineuronal net formation in juvenile mice. BMC Neurosci. 2018;19:41. doi: 10.1186/s12868-018-0442-z. PubMed DOI PMC

Gildawie KR, Honeycutt JA, Brenhouse HC. Region-specific Effects of Maternal Separation on Perineuronal Net and Parvalbumin-expressing Interneuron Formation in Male and Female Rats. Neuroscience. 2020;428:23–37. doi: 10.1016/j.neuroscience.2019.12.010. PubMed DOI

Murthy S, Kane GA, Katchur NJ, Lara Mejia PS, Obiofuma G, Buschman TJ, et al. Perineuronal nets, inhibitory interneurons, and anxiety-related ventral hippocampal neuronal oscillations are altered by early life adversity. Biol Psychiatry. 2019;85:1011–20. doi: 10.1016/j.biopsych.2019.02.021. PubMed DOI PMC

Guadagno A, Verlezza S, Long H, Wong TP, Walker CD. It is all in the right amygdala: increased synaptic plasticity and perineuronal nets in male, but not female, juvenile rat pups after exposure to early-life stress. J Neurosci. 2020;40:8276–91. doi: 10.1523/JNEUROSCI.1029-20.2020. PubMed DOI PMC

Pesarico AP, Bueno-Fernandez C, Guirado R, Gomez-Climent MA, Curto Y, Carceller H, et al. Chronic stress modulates interneuronal plasticity: effects on psa-ncam and perineuronal nets in cortical and extracortical regions. Front Cell Neurosci. 2019;13:197. doi: 10.3389/fncel.2019.00197. PubMed DOI PMC

Koskinen MK, van Mourik Y, Smit AB, Riga D, Spijker S. From stress to depression: development of extracellular matrix-dependent cognitive impairment following social stress. Sci Rep. 2020;10:17308. doi: 10.1038/s41598-020-73173-2. PubMed DOI PMC

Mennesson M, Orav E, Gigliotta A, Kulesskaya N, Saarnio S, Kirjavainen A, et al. Kainate receptor auxiliary subunit NETO2-related cued fear conditioning impairments associate with defects in amygdala development and excitability. eNeuro 2020;7. 10.1523/ENEURO.0541-19.2020. PubMed PMC

Lasek AW, Chen H, Chen WY. Releasing Addiction Memories Trapped in Perineuronal Nets. Trends Genet. 2018;34:197–208. doi: 10.1016/j.tig.2017.12.004. PubMed DOI PMC

Slaker ML, Jorgensen ET, Hegarty DM, Liu X, Kong Y, Zhang F, et al. Cocaine Exposure Modulates Perineuronal Nets and Synaptic Excitability of Fast-Spiking Interneurons in the Medial Prefrontal Cortex. eNeuro 2018;5. 10.1523/ENEURO.0221-18.2018. PubMed PMC

Gil-Miravet I, Guarque-Chabrera J, Carbo-Gas M, Olucha-Bordonau F, Miquel M. The role of the cerebellum in drug-cue associative memory: functional interactions with the medial prefrontal cortex. Eur J Neurosci. 2019;50:2613–22. doi: 10.1111/ejn.14187. PubMed DOI

Vazquez-Sanroman DB, Monje RD, Bardo MT. Nicotine self-administration remodels perineuronal nets in ventral tegmental area and orbitofrontal cortex in adult male rats. Addict Biol. 2017;22:1743–55. doi: 10.1111/adb.12437. PubMed DOI PMC

Saito M, Smiley JF, Hui M, Masiello K, Betz J, Ilina M, et al. Neonatal ethanol disturbs the normal maturation of parvalbumin interneurons surrounded by subsets of perineuronal nets in the cerebral cortex: partial reversal by lithium. Cereb Cortex. 2019;29:1383–97. doi: 10.1093/cercor/bhy034. PubMed DOI PMC

Chen H, He D, Lasek AW. Repeated binge drinking increases perineuronal nets in the insular cortex. Alcohol, Clin Exp Res. 2015;39:1930–8. doi: 10.1111/acer.12847. PubMed DOI PMC

Blacktop JM, Todd RP, Sorg BA. Role of perineuronal nets in the anterior dorsal lateral hypothalamic area in the acquisition of cocaine-induced conditioned place preference and self-administration. Neuropharmacology. 2017;118:124–36. doi: 10.1016/j.neuropharm.2017.03.018. PubMed DOI PMC

Blacktop JM, Sorg BA. Perineuronal nets in the lateral hypothalamus area regulate cue-induced reinstatement of cocaine-seeking behavior. Neuropsychopharmacology. 2019;44:850–8. doi: 10.1038/s41386-018-0212-8. PubMed DOI PMC

Vazquez-Sanroman D, Carbo-Gas M, Leto K, Cerezo-Garcia M, Gil-Miravet I, Sanchis-Segura C, et al. Cocaine-induced plasticity in the cerebellum of sensitised mice. Psychopharmacol. 2015;232:4455–67. doi: 10.1007/s00213-015-4072-1. PubMed DOI

Sanchez-Hernandez A, Nicolas C, Gil-Miravet I, Guarque-Chabrera J, Solinas M, Miquel M. Time-dependent regulation of perineuronal nets in the cerebellar cortex during abstinence of cocaine-self administration. Psychopharmacol. 2021;238:1059–68. doi: 10.1007/s00213-020-05752-0. PubMed DOI

Carbo-Gas M, Moreno-Rius J, Guarque-Chabrera J, Vazquez-Sanroman D, Gil-Miravet I, Carulli D, et al. Cerebellar perineuronal nets in cocaine-induced pavlovian memory: Site matters. Neuropharmacology. 2017;125:166–80. doi: 10.1016/j.neuropharm.2017.07.009. PubMed DOI

Vazquez-Sanroman D, Leto K, Cerezo-Garcia M, Carbo-Gas M, Sanchis-Segura C, Carulli D, et al. The cerebellum on cocaine: plasticity and metaplasticity. Addict Biol. 2015;20:941–55. doi: 10.1111/adb.12223. PubMed DOI

Van den Oever MC, Lubbers BR, Goriounova NA, Li KW, Van der Schors RC, Loos M, et al. Extracellular matrix plasticity and GABAergic inhibition of prefrontal cortex pyramidal cells facilitates relapse to heroin seeking. Neuropsychopharmacology. 2010;35:2120–33. doi: 10.1038/npp.2010.90. PubMed DOI PMC

Roura-Martinez D, Diaz-Bejarano P, Ucha M, Paiva RR, Ambrosio E, Higuera-Matas A. Comparative analysis of the modulation of perineuronal nets in the prefrontal cortex of rats during protracted withdrawal from cocaine, heroin and sucrose self-administration. Neuropharmacology. 2020;180:108290. doi: 10.1016/j.neuropharm.2020.108290. PubMed DOI

Xue Y-X, Xue L-F, Liu J-F, He J, Deng J-H, Sun S-C, et al. Depletion of perineuronal nets in the amygdala to enhance the erasure of drug memories. J Neurosci. 2014;34:6647–58. doi: 10.1523/JNEUROSCI.5390-13.2014. PubMed DOI PMC

Lubbers BR, Matos MR, Horn A, Visser E, Van der Loo RC, Gouwenberg Y, et al. The extracellular matrix protein brevican limits time-dependent enhancement of cocaine conditioned place preference. Neuropsychopharmacology. 2016;41:1907–16. doi: 10.1038/npp.2015.361. PubMed DOI PMC

Chen H, Lasek AW. Perineuronal nets in the insula regulate aversion-resistant alcohol drinking. Addict Biol. 2020;25:e12821. PubMed PMC

Dong Y, Nestler EJ. The neural rejuvenation hypothesis of cocaine addiction. Trends Pharm Sci. 2014;35:374–83. doi: 10.1016/j.tips.2014.05.005. PubMed DOI PMC

Bin Ibrahim MZ, Benoy A, Sajikumar S. Long-term plasticity in the hippocampus: maintaining within and ‘tagging’ between synapses. FEBS J. 2022;289:2176–201. PubMed

Harkness JH, Gonzalez AE, Bushana PN, Jorgensen ET, Hegarty DM, Di Nardo AA, et al. Diurnal changes in perineuronal nets and parvalbumin neurons in the rat medial prefrontal cortex. Brain Struct Funct. 2021;226:1135–53. doi: 10.1007/s00429-021-02229-4. PubMed DOI PMC

Miyata S, Komatsu Y, Yoshimura Y, Taya C, Kitagawa H. Persistent cortical plasticity by upregulation of chondroitin 6-sulfation. Nat Neurosci. 2012;15:414–22. doi: 10.1038/nn.3023. PubMed DOI

Lin R, Rosahl TW, Whiting PJ, Fawcett JW, Kwok JC. 6-Sulphated chondroitins have a positive influence on axonal regeneration. PloS One. 2011;6:e21499. doi: 10.1371/journal.pone.0021499. PubMed DOI PMC

Foscarin S, Raha-Chowdhury R, Fawcett JW, Kwok JCF. Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory. Aging. 2017;9:1607–22. doi: 10.18632/aging.101256. PubMed DOI PMC

D’Agostino A, Stellavato A, Corsuto L, Diana P, Filosa R, La Gatta A, et al. Is molecular size a discriminating factor in hyaluronan interaction with human cells? Carbohydr Polym. 2017;157:21–30. doi: 10.1016/j.carbpol.2016.07.125. PubMed DOI

Al’Qteishat A, Gaffney J, Krupinski J, Rubio F, West D, Kumar S, et al. Changes in hyaluronan production and metabolism following ischaemic stroke in man. Brain. 2006;129:2158–76. doi: 10.1093/brain/awl139. PubMed DOI

Cargill R, Kohama SG, Struve J, Su W, Banine F, Witkowski E, et al. Astrocytes in aged nonhuman primate brain gray matter synthesize excess hyaluronan. Neurobiol Aging. 2012;33:830.e813–824. doi: 10.1016/j.neurobiolaging.2011.07.006. PubMed DOI PMC

Sugitani K, Egorova D, Mizumoto S, Nishio S, Yamada S, Kitagawa H, et al. Hyaluronan degradation and release of a hyaluronan-aggrecan complex from perineuronal nets in the aged mouse brain. Biochimica et Biophysica Acta (BBA) - Gen Subj. 2021;1865:129804. doi: 10.1016/j.bbagen.2020.129804. PubMed DOI

Patrizi A, Awad PN, Chattopadhyaya B, Li C, Di Cristo G, Fagiolini M. Accelerated hyper-maturation of parvalbumin circuits in the absence of MeCP2. Cereb Cortex. 2020;30:256–68. doi: 10.1093/cercor/bhz085. PubMed DOI PMC

Pirbhoy PS, Rais M, Lovelace JW, Woodard W, Razak KA, Binder DK, et al. Acute pharmacological inhibition of matrix metalloproteinase-9 activity during development restores perineuronal net formation and normalizes auditory processing in Fmr1 KO mice. J Neurochem. 2020;155:538–58. doi: 10.1111/jnc.15037. PubMed DOI PMC

Berretta S, Pantazopoulos H, Markota M, Brown C, Batzianouli ET. Losing the sugar coating: potential impact of perineuronal net abnormalities on interneurons in schizophrenia. Schizophr Res. 2015;167:18–27. doi: 10.1016/j.schres.2014.12.040. PubMed DOI PMC

Cabungcal JH, Steullet P, Morishita H, Kraftsik R, Cuenod M, Hensch TK, et al. Perineuronal nets protect fast-spiking interneurons against oxidative stress. Proc Natl Acad Sci USA. 2013;110:9130–5. doi: 10.1073/pnas.1300454110. PubMed DOI PMC

Scholefield Z, Yates EA, Wayne G, Amour A, McDowell W, Turnbull JE. Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer’s beta-secretase. J Cell Biol. 2003;163:97–107. doi: 10.1083/jcb.200303059. PubMed DOI PMC

Liu CC, Zhao N, Yamaguchi Y, Cirrito JR, Kanekiyo T, Holtzman DM, et al. Neuronal heparan sulfates promote amyloid pathology by modulating brain amyloid-beta clearance and aggregation in Alzheimer’s disease. Sci Transl Med. 2016;8:332ra344. doi: 10.1126/scitranslmed.aad3650. PubMed DOI PMC

Goedert M, Jakes R, Spillantini MG, Hasegawa M, Smith MJ, Crowther RA. Assembly of microtubule-associated protein tau into Alzheimer-like filaments induced by sulphated glycosaminoglycans. Nature. 1996;383:550–3. doi: 10.1038/383550a0. PubMed DOI

Holmes BB, DeVos SL, Kfoury N, Li M, Jacks R, Yanamandra K, et al. Heparan sulfate proteoglycans mediate internalization and propagation of specific proteopathic seeds. Proc Natl Acad Sci USA. 2013;110:E3138–3147. doi: 10.1073/pnas.1301440110. PubMed DOI PMC

Suttkus A, Holzer M, Morawski M, Arendt T. The neuronal extracellular matrix restricts distribution and internalization of aggregated Tau-protein. Neuroscience. 2016;313:225–35. doi: 10.1016/j.neuroscience.2015.11.040. PubMed DOI

Baig S, Wilcock GK, Love S. Loss of perineuronal net N-acetylgalactosamine in Alzheimer’s disease. Acta Neuropathol. 2005;110:393–401. doi: 10.1007/s00401-005-1060-2. PubMed DOI

Crapser JD, Ochaba J, Soni N, Reidling JC, Thompson LM, Green KN. Microglial depletion prevents extracellular matrix changes and striatal volume reduction in a model of Huntington’s disease. Brain. 2020;143:266–88. doi: 10.1093/brain/awz363. PubMed DOI PMC

Crapser JD, Spangenberg EE, Barahona RA, Arreola MA, Hohsfield LA, Green KN. Microglia facilitate loss of perineuronal nets in the Alzheimer’s disease brain. EBioMedicine. 2020;58:102919. doi: 10.1016/j.ebiom.2020.102919. PubMed DOI PMC

Fu AK, Ip NY. Regulation of postsynaptic signaling in structural synaptic plasticity. Curr Opin Neurobiol. 2017;45:148–55. doi: 10.1016/j.conb.2017.05.016. PubMed DOI

Yang S, Cacquevel M, Saksida LM, Bussey TJ, Schneider BL, Aebischer P, et al. Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology. Exp Neurol. 2014;265CP:48–58. PubMed PMC

Tsilibary E, Tzinia A, Radenovic L, Stamenkovic V, Lebitko T, Mucha M, et al. Neural ECM proteases in learning and synaptic plasticity. Prog Brain Res. 2014;214:135–57. doi: 10.1016/B978-0-444-63486-3.00006-2. PubMed DOI

Rossi D, Gruart A, Contreras-Murillo G, Muhaisen A, Avila J, Delgado-Garcia JM, et al. Reelin reverts biochemical, physiological and cognitive alterations in mouse models of Tauopathy. Prog Neurobiol. 2020;186:101743. doi: 10.1016/j.pneurobio.2019.101743. PubMed DOI

Duncan JA, Foster R, Kwok JCF. The potential of memory enhancement through modulation of perineuronal nets. Br J Pharm. 2019;176:3611–21. doi: 10.1111/bph.14672. PubMed DOI PMC

Parvalbumin - Positive Neurons in the Neocortex: A Review

Perineuronal nets affect memory and learning after synapse withdrawal