Atypical perineuronal nets in the CA2 region interfere with social memory in a mouse model of social dysfunction
Open accessAbstract
Social memory dysfunction is an especially devastating symptom of many neuropsychiatric disorders, which makes understanding the cellular and molecular processes that contribute to such abnormalities important. Evidence suggests that the hippocampus, particularly the CA2 region, plays an important role in social memory. We sought to identify potential mechanisms of social memory dysfunction in the hippocampus by investigating features of neurons, glia, and the extracellular matrix (ECM) of BTBR mice, an inbred mouse strain with deficient social memory. The CA2 is known to receive inputs from dentate gyrus adult-born granule cells (abGCs), neurons known to participate in social memory, so we examined this cell population and found fewer abGCs, as well as fewer axons from abGCs in the CA2 of BTBR mice compared to controls. We also found that BTBR mice had fewer pyramidal cell dendritic spines, in addition to fewer microglia and astrocytes, in the CA2 compared to controls. Along with diminished neuronal and glial elements, we found atypical perineuronal nets (PNNs), specialized ECM structures that regulate plasticity, in the CA2 of BTBR mice. By diminishing PNNs in the CA2 of BTBR mice to control levels, we observed a partial restoration of social memory. Our findings suggest that the CA2 region of BTBR mice exhibits multiple cellular and extracellular abnormalities and identify atypical PNNs as one mechanism producing social memory dysfunction, although the contribution of reduced abGC afferents, pyramidal cell dendritic spine, and glial cell numbers remains unexplored.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PNNs play a distinct role in social memory.
“PNNs play a distinct role in social memory, since mice with deficient social memory (BTBR mice) have atypical PNNs, and their degradation can partially restore social memory [132].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [132]
PNN degradation can partially restore social memory in BTBR mice with deficient social memory.
“PNNs play a distinct role in social memory, since mice with deficient social memory (BTBR mice) have atypical PNNs, and their degradation can partially restore social memory [132].”
From The extracellular matrix and perineuronal nets in memory (2022) · cites this paper as [132]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Synaptic Pruning by Microglia Is Necessary for Normal Brain Development
Paolicelli, R. C., Bolasco, G., Pagani, F., Maggi, L., Scianni, M., Panzanelli, P., Giustetto, M., Ferreira, T. A., Guiducci, E., Dumas, L., et al. (2011) · Science · doi:10.1126/science.1202529 · Cited by 4,244 · see citing works
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089 · see citing works
Astrocytes mediate synapse elimination through MEGF10 and MERTK pathways
Chung, W.-S., Clarke, L. E., Wang, G. X., Stafford, B. K., Sher, A., Chakraborty, C., Joung, J., Foo, L. C., Thompson, A., Chen, C., et al. (2013) · Nature · doi:10.1038/nature12776 · Cited by 1,377 · see citing works
A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons
Tervo, D. G. R., Hwang, B., Viswanathan, S., Gaj, T., Lavzin, M., Ritola, K., Lindo, S. E., Michael, S. C., Кулешова, Е. П., Ojala, D. S., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.021 · Cited by 1,170 · see citing works
The hippocampal CA2 region is essential for social memory
Hitti, F. L., & Siegelbaum, S. A. (2014) · Nature · doi:10.1038/nature13028 · Cited by 976 · see citing works
Autism‐like behavioral phenotypes in BTBR T+tf/J mice
McFarlane, H. G., Kusek, G. K., Yang, M., Phoenix, J. L., Bolivar, V. J., & Crawley, J. N. (2008) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2007.00330.x · Cited by 812 · see citing works
Mouse behavioral tasks relevant to autism: Phenotypes of 10 inbred strains
MOY, S., NADLER, J., YOUNG, N., PEREZ, A., HOLLOWAY, L., BARBARO, R., BARBARO, J., WILSON, L., THREADGILL, D., & LAUDER, J. (2007) · Behavioural Brain Research · doi:10.1016/j.bbr.2006.07.030 · Cited by 776 · see citing works
Ventral CA1 neurons store social memory
Okuyama, T., Kitamura, T., Roy, D. S., Itohara, S., & Tonegawa, S. (2016) · Science · doi:10.1126/science.aaf7003 · Cited by 657 · see citing works
Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity
Nguyen, P. T., Dorman, L. C., Pan, S., Vainchtein, I. D., Han, R. T., Nakao-Inoue, H., Taloma, S. E., Barron, J. J., Molofsky, A. B., Kheirbek, M. A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.050 · Cited by 615 · see citing works
Cell type–specific genetic and optogenetic tools reveal hippocampal CA2 circuits
Kohara, K., Pignatelli, M., Rivest, A. J., Jung, H.-Y., Kitamura, T., Suh, J., Frank, D., Kajikawa, K., Mise, N., Obata, Y., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3614 · Cited by 528 · see citing works
On the Integration of Space, Time, and Memory
Eichenbaum, H. (2017) · Neuron · doi:10.1016/j.neuron.2017.06.036 · Cited by 512 · see citing works
Modulation of the proteoglycan receptor PTPσ promotes recovery after spinal cord injury
Lang, B. T., Cregg, J. M., DePaul, M. A., Tran, A. P., Xu, K., Dyck, S. M., Madalena, K. M., Brown, B. P., Weng, Y.-L., Li, S., et al. (2015) · Nature · doi:10.1038/nature13974 · Cited by 465 · see citing works
Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity
Sorg, B. A., Berretta, S., Blacktop, J. M., Fawcett, J. W., Kitagawa, H., Kwok, J. C. F., & Miquel, M. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2351-16.2016 · Cited by 454 · see citing works
The hippocampal sharp wave-ripple in memory retrieval for immediate use and consolidation
Joo, H. R., & Frank, L. M. (2018) · Nature Reviews Neuroscience · doi:10.1038/s41583-018-0077-1 · Cited by 430 · see citing works
Otx2 Binding to Perineuronal Nets Persistently Regulates Plasticity in the Mature Visual Cortex
Beurdeley, M., Spatazza, J., Lee, H. H. C., Sugiyama, S., Bernard, C., Di Nardo, A. A., Hensch, T. K., & Prochiantz, A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0394-12.2012 · Cited by 398 · see citing works
Social brain, social dysfunction and social withdrawal
Porcelli, S., van der Wee, N. J. A., van der Werff, S. J., Aghajani, M., Glennon, J. C., van Heukelum, S., Mogavero, F., Lobo, A., Olivera, F. J. N., Lobo, E., et al. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.012 · Cited by 397 · see citing works
Rediscovering area CA2: unique properties and functions
Dudek, S. M., Alexander, G. M., & Farris, S. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2015.22 · Cited by 329 · see citing works
A hippocampal circuit linking dorsal CA2 to ventral CA1 critical for social memory dynamics
Meira, T., Leroy, F., Buss, E. W., Oliva, A., Park, J., & Siegelbaum, S. A. (2018) · Nature Communications · doi:10.1038/s41467-018-06501-w · Cited by 310 · see citing works
Lensjø, K. K., Lepperød, M. E., Dick, G., Hafting, T., & Fyhn, M. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.2504-16.2016 · Cited by 281 · see citing works
Microglial Polarization and Inflammatory Mediators After Intracerebral Hemorrhage
Zhang, Z., Zhang, Z., Lu, H., Yang, Q., Wu, H., & Wang, J. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9785-6 · Cited by 276 · see citing works
Perineuronal Nets Suppress Plasticity of Excitatory Synapses on CA2 Pyramidal Neurons
Carstens, K. E., Phillips, M. L., Pozzo-Miller, L., Weinberg, R. J., & Dudek, S. M. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.0245-16.2016 · Cited by 271 · see citing works
Molecular signals of plasticity at the tetrapartite synapse
Dityatev, A., & Rusakov, D. A. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2010.12.006 · Cited by 267 · see citing works
Harada, K., Kamiya, T., & Tsuboi, T. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00499 · Cited by 246 · see citing works
Adult neurogenesis, glia, and the extracellular matrix
Cope, E. C., & Gould, E. (2019) · Cell Stem Cell · doi:10.1016/j.stem.2019.03.023 · Cited by 236 · see citing works
Self-citationTargeted activation of the hippocampal CA2 area strongly enhances social memory
Smith, A. S., Williams Avram, S. K., Cymerblit-Sabba, A., Song, J., & Young, W. S. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.189 · Cited by 236 · see citing works
Microglia Play an Active Role in Obesity-Associated Cognitive Decline
Cope, E. C., LaMarca, E. A., Monari, P. K., Olson, L. B., Martinez, S., Zych, A. D., Katchur, N. J., & Gould, E. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0789-18.2018 · Cited by 225 · see citing works
Self-citationLesions to the <scp>CA</scp>2 region of the hippocampus impair social memory in mice
Stevenson, E. L., & Caldwell, H. K. (2014) · European Journal of Neuroscience · doi:10.1111/ejn.12689 · Cited by 222 · see citing works
Haukvik, U. K., Tamnes, C. K., Söderman, E., & Agartz, I. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.08.012 · Cited by 220 · see citing works
Montagrin, A., Saiote, C., & Schiller, D. (2017) · Hippocampus · doi:10.1002/hipo.22797 · Cited by 197 · see citing works
The BTBR mouse model of idiopathic autism – Current view on mechanisms
Meyza, K. Z., & Blanchard, D. C. (2017) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.12.037 · Cited by 189 · see citing works
Stephenson, D. T., O'Neill, S. M., Narayan, S., Tiwari, A., Arnold, E., Samaroo, H. D., Du, F., Ring, R. H., Campbell, B., Pletcher, M., et al. (2011) · Molecular Autism · doi:10.1186/2040-2392-2-7 · Cited by 180 · see citing works
Choroid-Plexus-Derived Otx2 Homeoprotein Constrains Adult Cortical Plasticity
Spatazza, J., Lee, H. H. C., Di Nardo, A. A., Tibaldi, L., Joliot, A., Hensch, T. K., & Prochiantz, A. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.05.014 · Cited by 176 · see citing works
The hippocampus and depression
Sheline, Y. I., Mittler, B., & Mintun, M. A. (2002) · European Psychiatry · doi:10.1016/s0924-9338(02)00655-7 · Cited by 175 · see citing works
Lein, E. S., Callaway, E. M., Albright, T. D., & Gage, F. H. (2005) · Journal of Comparative Neurology · doi:10.1002/cne.20426 · Cited by 158 · see citing works
Impaired memory for faces and social scenes in autism: clinical implications of memory dysfunction
WILLIAMS, D., Goldstein, G., & Minshew, N. J. (2004) · Archives of Clinical Neuropsychology · doi:10.1016/j.acn.2002.08.001 · Cited by 148 · see citing works
Hylin, M. J., Orsi, S. A., Moore, A. N., & Dash, P. K. (2013) · Learning & Memory · doi:10.1101/lm.030197.112 · Cited by 143 · see citing works
Brain ageing changes proteoglycan sulfation, rendering perineuronal nets more inhibitory
Foscarin, S., Raha-Chowdhury, R., Fawcett, J. W., & Kwok, J. C. F. (2017) · Aging · doi:10.18632/aging.101256 · Cited by 139 · see citing works
Perineuronal net digestion with chondroitinase restores memory in mice with tau pathology
Yang, S., Cacquevel, M., Saksida, L. M., Bussey, T. J., Schneider, B. L., Aebischer, P., Melani, R., Pizzorusso, T., Fawcett, J. W., & Spillantini, M. G. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2014.11.013 · Cited by 138 · see citing works
Chondroitin sulfate proteoglycans inhibit oligodendrocyte myelination through PTPσ
Pendleton, J. C., Shamblott, M. J., Gary, D. S., Belegu, V., Hurtado, A., Malone, M. L., & McDonald, J. W. (2013) · Experimental Neurology · doi:10.1016/j.expneurol.2013.04.003 · Cited by 134 · see citing works
Dynamic microglial modulation of spatial learning and social behavior
Torres, L., Danver, J., Ji, K., Miyauchi, J. T., Chen, D., Anderson, M. E., West, B. L., Robinson, J. K., & Tsirka, S. E. (2015) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2015.09.001 · Cited by 126 · see citing works
In Sickness and in Health: Perineuronal Nets and Synaptic Plasticity in Psychiatric Disorders
Pantazopoulos, H., & Berretta, S. (2015) · Neural Plasticity · doi:10.1155/2016/9847696 · Cited by 118 · see citing works
del Zoppo, G. J., Frankowski, H., Gu, Y.-H., Osada, T., Kanazawa, M., Milner, R., Wang, X., Hosomi, N., Mabuchi, T., & Koziol, J. A. (2012) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2012.11 · Cited by 116 · see citing works
Low sociability in BTBR T+tf/J mice is independent of partner strain
Yang, M., Abrams, D. N., Zhang, J. Y., Weber, M. D., Katz, A. M., Clarke, A. M., Silverman, J. L., & Crawley, J. N. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.12.025 · Cited by 112 · see citing works
Loss of perineuronal net N-acetylgalactosamine in Alzheimer’s disease
Baig, S., Wilcock, G. K., & Love, S. (2005) · Acta Neuropathologica · doi:10.1007/s00401-005-1060-2 · Cited by 112 · see citing works
Monteiro, B. M. M., Moreira, F. A., Massensini, A. R., Moraes, M. F. D., & Pereira, G. S. (2013) · Hippocampus · doi:10.1002/hipo.22218 · Cited by 105 · see citing works
Yamada, J., Ohgomori, T., & Jinno, S. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.12792 · Cited by 99 · see citing works
Microglial modulation of neuronal activity in the healthy brain
York, E. M., Bernier, L., & MacVicar, B. A. (2018) · Developmental Neurobiology · doi:10.1002/dneu.22571 · Cited by 98 · see citing works
Hayani, H., Song, I., & Dityatev, A. (2018) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2018.00149 · Cited by 84 · see citing works
Novel connection between newborn granule neurons and the hippocampal CA2 field
Llorens-Martín, M., Jurado-Arjona, J., Avila, J., & Hernández, F. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2014.10.021 · Cited by 83 · see citing works
Genetic Otx2 mis-localization delays critical period plasticity across brain regions
Lee, H. H. C., Bernard, C., Ye, Z., Acampora, D., Simeone, A., Prochiantz, A., Di Nardo, A. A., & Hensch, T. K. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.1 · Cited by 82 · see citing works
Domínguez, S., Rey, C. C., Therreau, L., Fanton, A., Massotte, D., Verret, L., Piskorowski, R. A., & Chevaleyre, V. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.09.044 · Cited by 81 · see citing works
Circadian Rhythms of Perineuronal Net Composition
Pantazopoulos, H., Gisabella, B., Rexrode, L., Benefield, D., Yıldız, E., Seltzer, P., Valeri, J., Chelini, G., Reich, A., Ardelt, M., et al. (2020) · eNeuro · doi:10.1523/eneuro.0034-19.2020 · Cited by 73 · see citing works
Antonio, A. S., Liban, K., Ikrar, T., Tsyganovskiy, E., & Xu, X. (2013) · The Journal of Comparative Neurology · doi:10.1002/cne.23486 · Cited by 72 · see citing works
Miyata, S., & Kitagawa, H. (2016) · Neural Plasticity · doi:10.1155/2016/1305801 · Cited by 70 · see citing works
Novel role for mineralocorticoid receptors in control of a neuronal phenotype
McCann, K. E., Lustberg, D. J., Shaughnessy, E. K., Carstens, K. E., Farris, S., Alexander, G. M., Radzicki, D., Zhao, M., & Dudek, S. M. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0598-7 · Cited by 69 · see citing works
Daimon, C. M., Jasien, J., Wood, W. H., Zhang, Y., Becker, K. G., Silverman, J. L., Crawley, J. N., Martin, B., & Maudsley, S. R. (2015) · Frontiers in Physiology · doi:10.3389/fphys.2015.00324 · Cited by 67 · see citing works
Mak, E., Gabel, S., Su, L., Williams, G. B., Arnold, R., Passamonti, L., Vazquez Rodríguez, P., Surendranathan, A., Bevan-Jones, W. R., Rowe, J. B., et al. (2017) · International Psychogeriatrics · doi:10.1017/s1041610216002143 · Cited by 66 · see citing works
Seese, R. R., Maske, A. R., LYNCH, G. S., & Gall, C. M. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.13 · Cited by 62 · see citing works
Jones-Davis, D. M., Yang, M., Rider, E., Osbun, N. C., da Gente, G. J., Li, J., Katz, A. M., Weber, M. D., Sen, S., Crawley, J., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0061829 · Cited by 61 · see citing works
Regulation of synaptic plasticity in hippocampal area CA2
Carstens, K. E., & Dudek, S. M. (2019) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2018.07.008 · Cited by 55 · see citing works
Disruption of perineuronal nets increases the frequency of sharp wave ripple events
Sun, Z. Y., Bozzelli, P. L., Caccavano, A., Allen, M., Balmuth, J., Vicini, S., Wu, J., & Conant, K. E. (2017) · Hippocampus · doi:10.1002/hipo.22804 · Cited by 55 · see citing works
BTBR T+tf/J mice: Autism-relevant behaviors and reduced fractone-associated heparan sulfate
Blanchard, D. C., Defensor, E. B., Meyza, K. Z., Pobbe, R. L. H., Pearson, B. L., Bolivar, V. J., & Blanchard, R. J. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.06.008 · Cited by 54 · see citing works
Adult-Born Neurons in the Hippocampus Are Essential for Social Memory Maintenance
Cope, E. C., Waters, R. C., Diethorn, E. J., Pagliai, K. A., Dias, C. G., Tsuda, M. C., Cameron, H. A., & Gould, E. (2020) · eNeuro · doi:10.1523/eneuro.0182-20.2020 · Cited by 48 · see citing works
Self-citationInhibiting constitutive neurogenesis compromises long-term social recognition memory
Pereira-Caixeta, A. R., Guarnieri, L. D. O., Medeiros, D. D. C., Mendes, E. M. A. M., Ladeira, L. C. D., Pereira, M. T., Moraes, M. F. D., & Pereira, G. S. (2018) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2018.06.014 · Cited by 44 · see citing works
Garrett, L., Zhang, J., Zimprich, A., Niedermeier, K. M., Fuchs, H., Gailus-Durner, V., Hrabě de Angelis, M., Vogt Weisenhorn, D., Wurst, W., & Hölter, S. M. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00302 · Cited by 37 · see citing works
Provenzano, G., Corradi, Z., Monsorno, K., Fedrizzi, T., Ricceri, L., Scattoni, M. L., & Bozzi, Y. (2016) · Frontiers in Neuroscience · doi:10.3389/fnins.2016.00396 · Cited by 34 · see citing works
Vasopressin Inhibits LTP in the CA2 Mouse Hippocampal Area
Chafaï, M., Corbani, M., Guillon, G., & Desarménien, M. G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0049708 · Cited by 32 · see citing works
The Efficacy of Emotion Recognition Rehabilitation for People with Alzheimer’s Disease
García-Casal, J. A., Goñi-Imízcoz, M., Bartolomé, M. V. P., Soto‐Pérez, F., Smith, S. J., Calvo, S., & Franco, M. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-160940 · Cited by 32 · see citing works
Kurtz, M. M., Bronfeld, M. F., & Rose, J. S. (2012) · Psychiatry Research · doi:10.1016/j.psychres.2012.06.025 · Cited by 26 · see citing works
Pereira-Caixeta, A. R., Guarnieri, L. D. O., Pena, R. R., Dias, T. L., & Pereira, G. S. (2016) · Molecular Neurobiology · doi:10.1007/s12035-016-9922-2 · Cited by 25 · see citing works
Integrated analysis of miRNA and mRNA expression profiles in the brains of BTBR mice
Wang, M., He, J., Zhou, Y., Lv, N., Zhao, M., Wei, H., & Li, R. (2020) · International Journal of Developmental Neuroscience · doi:10.1002/jdn.10019 · Cited by 8 · see citing works
Yang, S., Gigout, S., Molinaro, A., Naito-Matsui, Y., Hilton, S., Foscarin, S., Nieuwenhuis, B., Verhaagen, J., Pizzorusso, T., Saksida, L. M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.01.03.894188 · Cited by 4 · see citing works
Flagged first, then by citations
1 of the 74 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [11]Stevenson EL, Caldwell HK. Lesions to the CA2 region of the hippocampus impair social memory in mice. Eur J Neurosci 2014; 40: 3294– 3301. 25131412 PMC4218870
- [23]Yamada J, Ohgomori T, Jinno S. Perineuronal nets affect parvalbumin expression in GABAergic neurons of the mouse hippocampus. Eur J Neurosci 2015; 41: 368– 378. 25411016
Cited by
Sorted by citations
The extracellular matrix and perineuronal nets in memory
Fawcett, J. W., Fyhn, M., Jendelova, P., Kwok, J. C. F., Ruzicka, J., & Sorg, B. A. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01634-3 · Cited by 169 · see citing works
Lupori, L., Totaro, V., Cornuti, S., Ciampi, L., Carrara, F., Grilli, E., Viglione, A., Tozzi, F., Putignano, E., Mazziotti, R. M., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112788 · Cited by 106 · see citing works
Wegrzyn, D., Juckel, G., & Faissner, A. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105482 · Cited by 73 · see citing works
Perineuronal Nets: Subtle Structures with Large Implications
Carceller, H., Gramuntell, Y., Klimczak, P., & Nácher, J. (2022) · The Neuroscientist · doi:10.1177/10738584221106346 · Cited by 48 · see citing works
The fate of interneurons, GABA A receptor sub‐types and perineuronal nets in Alzheimer's disease
Ali, A. B., Islam, A., & Constanti, A. (2022) · Brain Pathology · doi:10.1111/bpa.13129 · Cited by 47 · see citing works
How Stress Influences the Dynamic Plasticity of the Brain’s Extracellular Matrix
Laham, B. J., & Gould, E. (2022) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.814287 · Cited by 47 · see citing works
Self-citationChondroitin 4- O -sulfation regulates hippocampal perineuronal nets and social memory
Huang, H., Joffrin, A. M., Zhao, Y., Miller, G. M., Zhang, G. C., Oka, Y., & Hsieh‐Wilson, L. C. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2301312120 · Cited by 41 · see citing works
From molecules to behavior: Implications for perineuronal net remodeling in learning and memory
Sanchez, B., Kraszewski, P., Lee, S., & Cope, E. C. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.16036 · Cited by 37 · see citing works
Self-citationCope, E. C., Wang, S. H., Waters, R. C., Gore, I. R., Vasquez, B., Laham, B. J., & Gould, E. (2023) · Nature Communications · doi:10.1038/s41467-023-37248-8 · Cited by 31 · see citing works
Self-citationLi, X., Wu, X., Lu, T., Kuang, C., Si, Y., Zheng, W., Li, Z., & Xue, Y.-X. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063412 · Cited by 25 · see citing works
Alexander, G. M., Nikolova, V. D., Stöber, T. M., Gruzdev, A., Moy, S. S., & Dudek, S. M. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.1626-24.2024 · Cited by 24 · see citing works
Shih, Y., Alipio, J. B., & Sahay, A. (2023) · Neuron · doi:10.1016/j.neuron.2023.09.009 · Cited by 22 · see citing works
Parvalbumin interneuron-derived tissue-type plasminogen activator shapes perineuronal net structure
Lépine, M., Douceau, S., Devienne, G. F., Prunotto, P., Lenoir, S., Regnauld, C., Pouettre, E., Piquet, J., Lebouvier, L., Hommet, Y., et al. (2022) · BMC Biology · doi:10.1186/s12915-022-01419-8 · Cited by 19 · see citing works
Gong, H., Yao, L., Deng, S., Lv, K., Luo, J., Luo, Y., Du, Z., Wu, L.-F., Liu, T., Wang, X., et al. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107568 · Cited by 14 · see citing works
Whitebirch, A. C., Santoro, B., Barnett, A., Lisgaras, C. P., Scharfman, H. E., & Siegelbaum, S. A. (2023) · Journal of Neuroscience · doi:10.1523/jneurosci.2091-22.2023 · Cited by 13 · see citing works
Li, Q., Shi, Y., Li, X. O., Yang, Y., Zhang, X., Xu, L., Ma, Z., Lu, T., Xu, R., Fan, L., et al. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232315290 · Cited by 13 · see citing works
Matthiesen, M., Khlaifia, A., Steininger, C. F. D., Dadabhoy, M., Mumtaz, U., & Arruda-Carvalho, M. (2023) · Molecular Brain · doi:10.1186/s13041-023-01028-8 · Cited by 13 · see citing works
CA2 physiology underlying social memory
Oliva, A. (2022) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2022.102642 · Cited by 12 · see citing works
Silencing hippocampal CA2 reduces behavioral flexibility in spatial learning
Lehr, A. B., Hitti, F. L., Deibel, S. H., & Stöber, T. M. (2023) · Hippocampus · doi:10.1002/hipo.23521 · Cited by 11 · see citing works
Liu, P., Zhao, Y., Xiong, W., Pan, Y., Zhu, M., & Zhu, X. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.12.024 · Cited by 9 · see citing works
A circuit from the basolateral amygdala to hippocampal CA3 regulates social behavior
Li, M., Jiang, Y., & Sun, Q. (2025) · Current Biology · doi:10.1016/j.cub.2025.07.059 · Cited by 8 · see citing works
Blanco, I., Deasy, S., Amontree, M., Gabriel, M., Caccavano, A., Vicini, S., Glasgow, E., & Conant, K. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03007-y · Cited by 4 · see citing works
Targeting CA2 Perineuronal Nets Restores Recognition Memory and Theta Oscillations in Aged Mice
Mehak, S. F., Shivakumar, A. B., Jijimon, F., Gupta, A., Pillai, V. G., & Gangadharan, G. (2025) · Aging Cell · doi:10.1111/acel.70139 · Cited by 6 · see citing works
Sakata, J. T., Alonge, K. M., Diethorn, E. J., Krishnan, K., Milman, N., Ramsaran, A. I., Wan, X., & Sorg, B. A. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.1367-25.2025 · Cited by 6 · see citing works
Self-citationZinc-a2-Glycoprotein Acts as a Component of PNN to Protect Hippocampal Neurons from Apoptosis
Chang, K.-W., Lin, L., Cui, T., Zhao, H., Li, J., Liu, C., Gao, D., & Lu, S. (2023) · Molecular Neurobiology · doi:10.1007/s12035-023-03771-4 · Cited by 6 · see citing works
Identification of hippocampal area CA2 in hamster and vole brain
Siegler, P. N., Shaughnessy, E. K., Horman, B. M., Vierling, T. T., King, D. H., Patisaul, H. B., Huhman, K. L., Alexander, G. M., & Dudek, S. M. (2024) · The Journal of Comparative Neurology · doi:10.1002/cne.25603 · Cited by 6 · see citing works
Perineuronal Net Microscopy: From Brain Pathology to Artificial Intelligence
Николаевич, П. М., Egorchev, A. A., Musin, F., Lipachev, N., Melnikova, A. A., Gimadutdinov, R. M., Kashipov, A., Molotkov, D. A., Chickrin, D. E., & Aganov, A. V. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25084227 · Cited by 7 · see citing works
Perineuronal Nets: From Structure to Neurological Disorders
Li, X., Li, N., Zhao, P., Ren, D., Luo, B., & Zhou, T. G. (2023) · Current Medicinal Chemistry · doi:10.2174/0109298673258290231009111633 · Cited by 6 · see citing works
Jakovljević, A., Stamenković, V., Poleksić, J., Hamad, M. I. K., Reiss, G., Jakovčevski, I., & Anđjus, P. R. (2024) · Biomolecules · doi:10.3390/biom14040508 · Cited by 6 · see citing works
Introduction to the special issue on: A new view of hippocampal area CA2
Dudek, S. M., Alexander, G. M., & Farris, S. (2023) · Hippocampus · doi:10.1002/hipo.23514 · Cited by 5 · see citing works
Chaunsali, L., Li, J., Fleischel, E. J., Prim, C. E., Kasprzak, I., Jiang, S., Hou, S., Escalante, M., Cope, E. C., Olsen, M. L., et al. (2025) · Alzheimer s & Dementia · doi:10.1002/alz.70813 · Cited by 5 · see citing works
Self-citationRapid Eye Movement Sleep Consolidates Social Memory
Fan, J., Zhou, F., Zheng, J., & Xu, H. (2023) · Neuroscience Bulletin · doi:10.1007/s12264-023-01080-3 · Cited by 4 · see citing works
Riemersma, I. W., Ike, K. G. O., Sollie, T., Meijer, E. L., Havekes, R., & Kas, M. J. (2024) · Cerebral Cortex · doi:10.1093/cercor/bhae136 · Cited by 3 · see citing works
Gore, I. R., Brown, C. J., Waters, R. C., & Gould, E. (2024) · Learning & Memory · doi:10.1101/lm.053968.124 · Cited by 3 · see citing works
Self-citationShi, Z., Qin, J., Gao, L., Fa, H., Wei, W., Zhao, T., Song, X., & Guo, X. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.106148 · Cited by 2 · see citing works
Nami, M., Wang, D. O., Panel, M.-N., Abel, T. G., Banerjee, S., Bredy, T. W., Chaudhury, D., Frankland, P. W., Hayashi, Y., Hirase, H., et al. (2026) · Molecular Brain · doi:10.1186/s13041-026-01281-7 · Cited by 2 · see citing works
Involvement of Kir4.1 in pain insensitivity of the BTBR mouse model of autism spectrum disorder
Li, X., Li, Q., Xu, L., Ma, Z., Shi, Y., Zhang, X., Yang, Y., Wang, J., Fan, L., & Wu, L. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2023.166700 · Cited by 2 · see citing works
Singh, A. P., Fromandi, M. B., Pimentel-Alarcón, D., Werling, D. M., Gasch, A. P., & Yu, J. J. (2024) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2024.100430 · Cited by 2 · see citing works
Developmental CA2 perineuronal net reduction restores social memory in Shank3 mutant mice
Diethorn, E. J., Rathaur, A. B., Lopez, B. R. R., Eke, C. K., & Gould, E. (2026) · Communications Biology · doi:10.1038/s42003-026-10338-1 · Cited by 2 · see citing works
Self-citationDudek, S. M. (2026) · Hippocampus · doi:10.1002/hipo.70068 · Cited by 1 · see citing works
Developmental Scarcity Induces Sex Differences in Social Recognition and CA2 Perineuronal Nets
Waters, R. C., Gore, I. R., Brown, C. J., Skweres-Gilmartin, A. L., Rathaur, A. B., & Gould, E. (2026) · eNeuro · doi:10.1523/eneuro.0199-26.2026 · Cited by 1 · see citing works
Self-citationBreach, M. R., Schatz, B., Akouri, H. E., Tapp, Z. M., Lastra, A. Z., Weinstein, A. E., Mohamed, M., Walters, A. E., Mohamed, R., Toirov, O., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-41521-3 · Cited by 1 · see citing works
Neurobiological mechanisms of social recognition memory
Park, G., & Lee, Y. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15754-7.00027-4
Representations of social experience in hippocampal circuits
Clein, R. S., & Gould, E. (2025) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2025.09.011
Self-citationSocial interaction mitigates cognitive impairments and tau pathology in socially isolated aged mice
Zeng, J., Bao, Z., Huang, W., Fu, A., Liang, Z., & Zhu, H. (2025) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823251394408
Chondroitin 4-sulphate depletion enhances synaptic plasticity and memory in agingPreprint
Burianova, J. S., Svoboda, J., Růžička, J., Štěpánková, K., Klausová, T., Gmiterková, L., Spundova, T., Martínez-Varea, N., Králíková, M., Tureček, R., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.01.28.702127
Bapat, V. A., Waters, R. C., Gordon, J. K., & Gould, E. (2026) · Neurobiology of Stress · doi:10.1016/j.ynstr.2026.100788
Self-citationEngel, D., & Nguyen, L. (2026) · STAR Protocols · doi:10.1016/j.xpro.2026.104470
Perineuronal Nets in Neuropsychiatric Disorders
Sikder, S., & Bozdagi-Gunal, O. (2026) · Brain Science Advances · doi:10.26599/bsa.2026.905017
- Authors
- Cope, E. C., Zych, A. D., Katchur, N. J., Waters, R. C., Laham, B. J., Diethorn, E. J., Park, C. Y., Meara, W. R., & Gould, E.
- Affiliations
- Princeton University (US)
- Corresponding author
- Gould, Elizabeth
- Venue
- Molecular Psychiatry
- Published
- 2021-06-28
- Volume
- 27
- Issue
- 8
- Pages
- 3520-3531
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC8712624
- OpenAlex
- W3177308468
- Cited by
- 49
- References
- 74
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 10 · 2023: 13 · 2022: 9
- FWCI
- 3.69
- Type
- journal article
- Language
- en
- Update notices
- correction (2022-04-22)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (MH118631-01)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- perineuronal nets, social memory, BTBR mice, social dysfunction, adult neurogenesis, dentate gyrus granule cells, dendritic spines, microglia, astrocytes, extracellular matrix
- MeSH terms
- Animals, Extracellular Matrix, Hippocampus, Mice, Inbred C57BL, Neuroglia, Neurons, Pyramidal Cells, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
