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Shank3 Deficiency Induces NMDA Receptor Hypofunction via an Actin-Dependent Mechanism
Open accessAbstract
Shank3, which encodes a scaffolding protein at glutamatergic synapses, is a genetic risk factor for autism. In this study, we examined the impact of Shank3 deficiency on the NMDA-type glutamate receptor, a key player in cognition and mental illnesses. We found that knockdown of Shank3 with a small interfering RNA (siRNA) caused a significant reduction of NMDAR-mediated ionic or synaptic current, as well as the surface expression of NR1 subunits, in rat cortical cultures. The effect of Shank3 siRNA on NMDAR currents was blocked by an actin stabilizer, and was occluded by an actin destabilizer, suggesting the involvement of actin cytoskeleton. Since actin dynamics is regulated by the GTPase Rac1 and downstream effector p21-activated kinase (PAK), we further examined Shank3 regulation of NMDARs when Rac1 or PAK was manipulated. We found that the reducing effect of Shank3 siRNA on NMDAR currents was mimicked and occluded by specific inhibitors for Rac1 or PAK, and was blocked by constitutively active Rac1 or PAK. Immunocytochemical data showed a strong reduction of F-actin clusters after Shank3 knockdown, which was occluded by a PAK inhibitor. Inhibiting cofilin, the primary downstream target of PAK and a major actin depolymerizing factor, prevented Shank3 siRNA from reducing NMDAR currents and F-actin clusters. Together, these results suggest that Shank3 deficiency induces NMDAR hypofunction by interfering with the Rac1/PAK/cofilin/actin signaling, leading to the loss of NMDAR membrane delivery or stability. It provides a potential mechanism for the role of Shank3 in cognitive deficit in autism.
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“Rac1 has been identified as a converging factor downstream of numerous proteins encoded by high-risk ASD genes, such as SHANK 4–6, FMR1 (fragile X mental retardation-1) 7, 8, NRXN 9, and AUTS2 10.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [4]
In the citing paper
“In mice, both congenital knockout and haploinsufficiency of Shank3 leads to diminished social interest in others and is associated with the disruption of cortical and subcortical circuits thought to be involved in ASD 22–26 and its ontogenesis 22,25,27,28.”
From Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time (2021) · cites this paper as [24]
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“These mutations are also often related to excitatory synaptic dysfunction and neurotransmission that may be potentially restorable 24,29,30.”
From Reduced sociability and social agency encoding in adult Shank3-mutant mice are restored through gene re-expression in real time (2021) · cites this paper as [24]
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“Although the size of the deleted region varies, the SHANK3 gene is nearly always included.”
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Harony-Nicolas, H., Kay, M., Hoffmann, J. D., Klein, M. E., Bozdagi-Gunal, O., Riad, M., Daskalakis, N. P., Sonar, S., Castillo, P. E., Hof, P. R., et al. (2017) · eLife · doi:10.7554/elife.18904 · Cited by 168
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Autism Spectrum Disorder: Focus on Glutamatergic Neurotransmission
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“Rac1 has been identified as a converging factor downstream of numerous proteins encoded by high-risk ASD genes, such as SHANK 4–6 , FMR1 (fragile X mental retardation-1) 7, 8 , NRXN 9 , and AUTS2 10 .”
Neural Mechanisms Underlying Repetitive Behaviors in Rodent Models of Autism Spectrum Disorders
Gandhi, T., & Lee, C. C. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2020.592710 · Cited by 97
Rho GTPases in Intellectual Disability: From Genetics to Therapeutic Opportunities
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“treatment with EHT1864 reduces NMDAR density in rat cortical cultures [226] and decreases density of dendritic spines in coltured hippocampal pyramidal neurons [227].”
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Zhu, L., 昆明650500，中国, 云., Zhu, Y., Gu, L., & Cheng, Y. (2021) · 动物学研究 · doi:10.24272/j.issn.2095-8137.2021.251 · Cited by 91
Modulation of actin dynamics by Rac1 to target cognitive function
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“For instance, rescue of NMDA receptor hypofunction with an actin stabilizer after knockdown of Shank3 in cultured rat cortical neurons suggests that some of the synaptic defects are due to disrupted cytoskeleton signaling (Duffney et al., 2013).”
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“At WT synapses, SHANK3 has been shown to enhance the localization and stabilization of synaptic NMDAR expression by crosslinking NMDAR/PSD95 complexes with the underlying actin cytoskeleton (Naisbitt et al., 1999; Duffney et al., 2013).”
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“Given that NMDAR function is an important target for dynamic regulation and fine-tuning for normal brain development and function (53, 74), our results suggest that NMDAR dysfunctions observed in many other animal models of ASD (71, 75-90) may need to be further examined for their temporal changes.”
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Self-citationDeficiency of Shank2 causes mania-like behavior that responds to mood stabilizers
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“…play a role in ASD and other neurodevelopmental disorders (for recent reviews, see Burnashev et al. 2015; Lee et al. 2015), including reports that autism candidate genes, such as NEUROLIGIN-1 and SHANK3, serve as regulators of NMDA receptor function (Budreck et al. 2013; Duffney et al. 2013).”
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“polymerization induces a rapid loss of synaptic scaffolding molecules and synaptic currents (Allison et al., 2000; Zhou et al., 2001; Kuriu et al., 2006; Duffney et al., 2013).”
BackgroundCofilin as a Promising Therapeutic Target for Ischemic and Hemorrhagic Stroke
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Neuronal L-Type Calcium Channel Signaling to the Nucleus Requires a Novel CaMKIIα-Shank3 Interaction
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“While Shank3 knockdown has been shown to disrupt NMDAR-mediated postsynaptic currents and DHPG-induced LTD (Verpelli et al., 2011; Duffney et al., 2013), roles of specific protein interactions with Shank3 are poorly understood.”
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“At wildtype synapses, Shank3 has been shown to increase the localisation and stabilisation of synaptic NMDARs by crosslinking NMDAR/PSD95 complexes with the underlying actin cytoskeleton [18, 48].”
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“Previous studies by several groups, including us, have shown that the trafficking and function of NMDARs are dependent on the integrity of actin cytoskeleton (Rosenmund and Westbrook, 1993; Allison et al., 1998; Gu et al., 2005; Duffney et al., 2013).”
BackgroundMethodInfluentialSelf-citationSpecific Roles of NMDA Receptor Subunits in Mental Disorders
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“Shank3 knockdown with a small-interfering RNA (siRNA) caused significant reductions of ionic or synaptic currents via NMDA receptors and reduced surface GluR1 expressions in rat cortical cultures [130].”
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“In addition, NMDAR and glutamate abnormalities have been identified in various brain disorders, such as major depressive disorder [16,17] and ASD [18-20], which are characterized by negative symptom domains.”
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“RAC1: RAC1 is a key regulator of neurite elongation, axon migration, synaptic function, and synaptic plasticity, as it promotes neurite outgrowth [85], spine formation and stabilization [87], and clustering of AMPA and NMDA receptors in the postsynaptic membrane [83,88], and it is essential for long-term synaptic plas…”
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“In addition, it is interesting to point out that p21-activated kinase (PAK) has been shown to interact with the protein SHANK3 in rat, whose disruption can also cause ASD, with mutant Shank3 altering actin dynamics driven by PAK signalling [51].”
BackgroundEffects of Trace Metal Profiles Characteristic for Autism on Synapses in Cultured Neurons
Hagmeyer, S., Mangus, K., Boeckers, T. M., & Grabrucker, A. M. (2015) · Neural Plasticity · doi:10.1155/2015/985083 · Cited by 39
“Mutations in the three family members Shank1, Shank2 (ProSAP1), and Shank3 (ProSAP2) have been described to be associated with ASD [46, 47] and animal models with deletions of these genes displaying ASD like phenotypes [48, 49].”
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“The delivery and stability of glutamate recep590 tors at synapses are dependent on the dynamics of 591 actin cytoskeleton [12, 27, 42, 53], which is dynam592 ically controlled by cofilin and other actin binding 593 proteins [54, 55].”
Self-citationBreckpot, J., Vercruyssen, M., Weyts, E., Vandevoort, S., D'Haenens, G., Buggenhout, G. V., Leempoels, L., Brischoux‐Boucher, E., Maldergem, L. V., Renieri, A., et al. (2016) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2016.08.003 · Cited by 33
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“Membrane delivery and stability of NMDARs depend on the integrity of the actin cytoskeleton [10].”
BackgroundScheefhals, N., Catsburg, L. A. E., Westerveld, M. L., Blanpied, T. A., Hoogenraad, C. C., & MacGillavry, H. D. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.08.102 · Cited by 32
“Glutamatergic transmission in general is reduced in Shank knockdown neurons (Arons et al., 2012; Duffney et al., 2013; Verpelli et al., 2011), Shank knockout mouse models (Bozdagi et al.”
BackgroundGlutamatergic candidate genes in autism spectrum disorder: an overview
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DIXDC1 Phosphorylation and Control of Dendritic Morphology Are Impaired by Rare Genetic Variants
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A kinome-wide RNAi screen identifies ERK2 as a druggable regulator of Shank3 stability
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“To support this conclusion, it was found that both behavioral deficits and NMDA receptor malfunction were rescued by restoring Rac1/PAK activity in these mice [16, 45].”
BackgroundEnlarged dendritic spines and pronounced neophobia in mice lacking the PSD protein RICH2
Sarowar, T., Grabrucker, S., Föhr, K. J., Mangus, K., Eckert, M., Bockmann, J., Boeckers, T. M., & Grabrucker, A. M. (2016) · Molecular Brain · doi:10.1186/s13041-016-0206-6 · Cited by 32
“in dendritic spines [32].”
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Self-citationNeurodevelopmental Consequences of Dietary Zinc Deficiency: A Status Report
Ross, M. M., Hernández-Espinosa, D. R., & Aizenman, E. (2023) · Biological Trace Element Research · doi:10.1007/s12011-023-03630-2 · Cited by 31
“Thus, Shank is hypothesized to mediate cytoskeletal changes and surface receptor trafficking and stabilization in response to stimuli like zinc [187].”
BackgroundCarey, C., Singh, N., Dunn, J., Sementa, T., Méndez, M. A., Velthuis, H., Pereira, A. C., Pretzsch, C. M., Horder, J., Hader, S., et al. (2022) · Translational Psychiatry · doi:10.1038/s41398-022-02143-1 · Cited by 33
“Shank3 encodes a scaffolding protein located at glutamatergic synapses [41, 42] and intracellular Shank proteins are involved in second messenger communication between mGluR5 and NMDA receptors [43].”
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“A recent report used small interfering RNAs (siRNA) to knock down expression of Shank3 in cultured cortical rat neurons and found a significant reduction in NMDA receptor-mediated synaptic currents.(54) Interestingly, the effects of Shank3 knockdown on NMDAR currents were abolished in the presence of Phalloidin, and o…”
BackgroundAli, F., Shao, L.-X., Gerhard, D. M., Sweasy, K., Pothula, S., Pittenger, C., Duman, R. S., & Kwan, A. C. (2020) · Molecular Psychiatry · doi:10.1038/s41380-020-0708-6 · Cited by 25
“22 typically measured by counting functional NMDARs [12, 58] and recording postsynaptic potentials [13].”
BackgroundLee, K., Jung, Y., Vyas, Y., Skelton, I., Abraham, W. C., Hsueh, Y., & Montgomery, J. M. (2022) · Molecular Autism · doi:10.1186/s13229-022-00494-6 · Cited by 24
“This is evident in Tbr1 deficient mice where Grin2b expression is decreased [36], and amygdalar neurons of Tbr1+/− mice fail to show neuronal activationinduced upregulation of Grin2b expression and impaired NMDAR function at thalamic-amygdalar synapses [14, 37–39]. d-cycloserine, a partial agonist of NMDARs, has been…”
BackgroundInfluentialSchlienger, S., Yam, P. T., Balekoglu, N., Ducuing, H., Michaud, J.-F., Makihara, S., Kramer, D. A., Chen, B., Fasano, A. A., Berardelli, A., et al. (2023) · Science Advances · doi:10.1126/sciadv.add5501 · Cited by 24
Dera, H. S. A. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112688 · Cited by 26
Shank3B mutant mice display pitch discrimination enhancements and learning deficits
Rendall, A. R., Perrino, P. A., Buscarello, A. N., & FITCH, R. H. (2018) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2018.10.003 · Cited by 25
Postsynaptic Proteins at Excitatory Synapses in the Brain—Relationship with Depressive Disorders
Samojedny, S., Czechowska, E., Pańczyszyn-Trzewik, P., & Sowa-Kućma, M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms231911423 · Cited by 22
“showed that Shank-3 knockdown using si-RNA in cortical structures resulted in decreased NMDAR-mediated ionic current and decreased GluN1 subunit expression, significantly confirming the importance of Shank3 in correct excitatory synapse function [110].”
Backgroundvan der Kooij, M. A., Masana, M., Rust, M. B., & Müller, M. B. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.12.001 · Cited by 23
Sungur, A. Ö., Stemmler, L., Wöhr, M., & Rust, M. B. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00025 · Cited by 22
“Moreover, some of the strongest candidate genes known to be involved modulate assembly or disassembly of F-actin (Reeve et al., 2005; Durand et al., 2012; Duffney et al., 2013, 2015; Steinecke et al., 2014; Peykov et al., 2015).”
BackgroundNovel functions for ADF/cofilin in excitatory synapses - lessons from gene-targeted mice
Rust, M. B. (2015) · Communicative & Integrative Biology · doi:10.1080/19420889.2015.1114194 · Cited by 18
Miozzo, F., Murru, L., Maiellano, G., di Iasio, I., Zippo, A. G., Avendano, A. Z., Metodieva, V. D., Riccardi, S., D’Aliberti, D., Spinelli, S., et al. (2024) · Journal of Neuroscience · doi:10.1523/jneurosci.0491-24.2024 · Cited by 18
Targeting Shank3 deficiency and paresthesia in autism spectrum disorder: A brief review
Huang, M., Qi, Q., & Xu, T. (2023) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2023.1128974 · Cited by 21
The gut-brain vagal axis scales hippocampal memory processes and plasticity
Onimus, O., Arrivet, F., Souza, I. N. D. O., Bertrand, B., Castel, J., Luquet, S. H., Mothet, J., Heck, N., & Gangarossa, G. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106569 · Cited by 17
LIMK1/2 in the mPFC Plays a Role in Chronic Stress-Induced Depressive-Like Effects in Mice
Gao, T., Wang, Y., Liu, L., Wang, J., Wang, Y., Guan, W., Chen, T., Zhao, J., & Jiang, B. (2020) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyaa067 · Cited by 17
Ryu, J. R., Jang, M. J., Jo, Y., Joo, S., Lee, D. H., Lee, B. Y., Nam, Y., & Sun, W. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.03.027 · Cited by 17
Li, C., Schaefer, M. L., Gray, C., Yang, Y., Furmanski, O., Liu, S., Worley, P. F., Mintz, C. D., Tao, F., & Johns, R. A. (2016) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2016.11.002 · Cited by 17
Gatford, N. J. F., Deans, P. J. M., Duarte, R. R. R., Chennell, G., Sellers, K. J., Raval, P., & Srivastava, D. P. (2021) · Human Molecular Genetics · doi:10.1093/hmg/ddab277 · Cited by 16
“Shank3 haploinsufficiency influences neurite outgrowth in human neurons (20) and has previously been shown to localize to growth cones (40,41).”
BackgroundInfluentialClinical profiling of MRD48 and functional characterization of two novel pathogenic RAC1 variants
Priolo, M., Zara, E., Radio, F. C., Ciolfi, A., Spadaro, F., Bellacchio, E., Mancini, C., Pantaleoni, F., Cordeddu, V., Chiriatti, L., et al. (2023) · European Journal of Human Genetics · doi:10.1038/s41431-023-01351-7 · Cited by 15
Jung, S. H., Hatcher-Solis, C. N., Moore, R. J., Bechmann, N. A., Harshman, S. W., Martin, J. L., & Jankord, R. (2019) · eNeuro · doi:10.1523/eneuro.0311-19.2019 · Cited by 15
“Recently, Duffney et al. (2013) showed that SHANK3 is associated with NMDA receptor function, suggesting a potential role for SHANK3 in learning and memory.”
BackgroundLoss of CC2D1A in Glutamatergic Neurons Results in Autistic-Like Features in Mice
Yang, C.-Y., Hung, Y.-C., Cheng, K., Ling, P., & Hsu, K. (2021) · Neurotherapeutics · doi:10.1007/s13311-021-01072-z · Cited by 14
Wang, W., Tan, T., Cao, Q., Zhang, F., Rein, B. A., Duan, W., & Yan, Z. (2022) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyac048 · Cited by 16
“…phenotypes could be attributed to the disrupted E/I balance (Lee et al., 2017; Antoine et al., 2019; Qin et al., 2021b), glutamatergic function (Duffney et al., 2013; Qin et al., 2018; Wang et al., 2018; Rapanelli et al., 2021), or GABA system (Jung et al., 2017; Lee et al., 2021; Rein et al.,…”
BackgroundSelf-citationSK Channel Modulates Synaptic Plasticity by Tuning CaMKIIα/β Dynamics
Shrestha, A., Sultana, R., Lee, C. C., & Ogundele, O. M. (2019) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2019.00018 · Cited by 13
“…disorder, bipolar depression, and schizophrenia (Seillier and Giuffrida, 2009; Uchino et al., 2010; Gustin et al., 2011; Namba et al., 2011; Ramsey et al., 2011; Anticevic et al., 2012; Duffney et al., 2013; Snyder and Gao, 2013; Aow et al., 2015; Stein et al., 2015; Ogundele and Lee, 2018).”
Deficits in integrative NMDA receptors caused by Grin1 disruption can be rescued in adulthood
Venkatesan, S., Binko, M. A., Mielnik, C. A., Ramsey, A. J., & Lambe, E. K. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01619-y · Cited by 13
Evaluating the association between the SHANK3 gene and bipolar disorder
Zhang, C., Wu, Z., Hong, W., Peng, D., & Fang, Y. (2016) · Psychiatry Research · doi:10.1016/j.psychres.2016.07.058 · Cited by 13
Wang, X., Guo, Z., Mei, D., Zhang, Y., Zhao, S., Hu, S., Luo, S., Wang, Q., & Gao, C. (2022) · Neurochemical Research · doi:10.1007/s11064-022-03554-8 · Cited by 13
“Shank3 deficiency can induce NMDA receptor hypofunction [23].”
BackgroundDbo/Henji Modulates Synaptic dPAK to Gate Glutamate Receptor Abundance and Postsynaptic Response
Wang, M., Chen, P., Wang, C.-H., Lai, T.-T., Tsai, P.-I., Cheng, Y.-J., Kao, H.-H., & Chien, C. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006362 · Cited by 10
“In mammalian systems, PAKs participate in many synaptic events including dendrite morphogenesis [47, 48], neurotransmitter receptor trafficking [49, 50], synaptic strength modulation [51], and activity-dependent plasticity [52].”
Emerging role of synaptic actin-regulatory pathway in the pathophysiology of mood disorders
Choi, S., & Han, K. (2015) · Animal Cells and Systems · doi:10.1080/19768354.2015.1086435 · Cited by 12
“It is notable that NMDA receptors are linked to actin cytoskeleton through actin binding proteins (Wyszynski et al. 1997), and that synaptic delivery and stability of NMDA receptors are dependent on both F-actin and Shank3 levels (Allison et al. 1998; Duffney et al. 2013).”
BackgroundInfantile spasms-linked Nedd4-2 mediates hippocampal plasticity and learning via cofilin signaling
Lee, K. Y., Zhu, J., Cutia, C. A., Christian, C. A., Rhodes, J. S., & Tsai, N. (2021) · EMBO Reports · doi:10.15252/embr.202152645 · Cited by 10
“…the incubations of control TAT, non-phosphorylated TAT-S3 or the phosphorylated TAT-pS3 peptides (10 µ M) for 12 – 16 h, as previously described (Duffney et al , 2013), in Nedd4-2 WT or Nedd4-2 cKO hippocampal neuron cultures on DIV 14-17, we measured the number of synaptic puncta and…”
Choudhary, A., Rosh, I., Hussein, Y., Netser, S., Shemen, A., Suliman, T., Rike, W. A., Simchi, L., Shklyar, B., Abu-Akel, A. M., et al. (2026) · Cell Death and Disease · doi:10.1038/s41419-026-08474-x · Cited by 11
Molecular Handoffs in Nitrergic Neurotransmission
Chaudhury, A. (2014) · Frontiers in Medicine · doi:10.3389/fmed.2014.00008 · Cited by 10
Efficacity of tDCS in catatonic patients with Phelan McDermid syndrome, a case series
Moyal, M., Plaze, M., Baruchet, A., Attali, D., Cravero, C., Raffin, M., Consoli, A., Cohen, D., Haroche, A., & Chaumette, B. (2022) · Brain stimulation · doi:10.1016/j.brs.2022.10.005 · Cited by 10
“SHANK3 encodes a scaffolding protein of the postsynaptic density of glutamatergic excitatory synapses and its deficiency induces NMDA receptor (NMDAR) hypofunctionality [7].”
BackgroundDifferential Gene Expression in Post-Finasteride Syndrome Patients
Howell, S., Song, W., Pastuszak, A. W., & Khera, M. (2021) · The Journal of Sexual Medicine · doi:10.1016/j.jsxm.2021.05.009 · Cited by 11
“59 Taken together, over-expression of APOE, GRIN2A, and TIAM1 likely results in increased function of the NMDA receptor and increased nervous system development through neurogenesis.”
Nardi, L., Chhabra, S., Leukel, P., Krueger‐Burg, D., Sommer, C., & Schmeißer, M. J. (2023) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2023.1199097 · Cited by 11
“As already known from previous studies (28), knockdown of SHANK3 is associated to NMDA receptor reduction and hypofunction.”
Ntoulas, G., Brakatselos, C., Nakas, G., Asprogerakas, M.-Z., Delis, F., Leontiadis, L. J., Trompoukis, G., Papatheodoropoulos, C., Gkikas, D., Valakos, D., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-02815-0 · Cited by 13
“Relative expression levels of the DEGs implicated in both the glutamatergic and GABAergic synapse pathways, allowing for comparative analysis of gene expression changes between the two pathways ( i ).”
BackgroundSynaptic Deficits in Adnp‐ Mutant Mice Are Ameliorated by Histone Demethylase LSD1 Inhibition
Lin, C., Ren, Y., Tam, K. W., Conrow‐Graham, M., & Yan, Z. (2025) · Autism Research · doi:10.1002/aur.70069 · Cited by 8
“SHANK3 deficiency specifically impairs NMDAR function in PFC (Duffney et al. 2013, 2015; Qin et al. 2018).”
Self-citationNMDAR dysfunction in autism spectrum disorders: Lessons learned from 10 years of study
Lee, S., Moon, H., & Kim, E. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103023 · Cited by 7
“Studies on mouse models of ASD, carrying ASD-risk genetic mutations, further revealed that NMDAR functions are dysregulated in these animals [9 e 12], and, in some animals, their correction can normalize ASD-like behavioral deficits [7,13,14].”
Mehrotra, S., Pierce, M. L., Dravid, S. M., & Murray, T. F. (2022) · Marine Drugs · doi:10.3390/md20090559 · Cited by 5
“Inhibition of PAK1 leads to a decrease in basal NMDAR currents [105].”
BackgroundDisrupted Development of the mPFC-Thalamic Circuit in Shank3–/– mice, an autism-associated model
Devienne, G. F., Vantomme, G., & Huguenard, J. R. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03390-6 · Cited by 3
“This fi nding is consistent with the known alterations in NMDA receptor-mediated neurotransmission in other Shank3 loss of function models [56, 62], where NMDA signaling is disrupted.”
Absence seizures and sleep–wake abnormalities in a rat model of GRIN2B neurodevelopmental disorder
Hristova, K., Fasol, M., McLaughlin, N., Nawaz, M., Taşkıran, M., Buller‐Peralta, I., Harris, A. P., Sutherland, A., Bassi, A., Ocampo-Garcés, A., et al. (2025) · Epilepsia · doi:10.1111/epi.18606 · Cited by 3
Positive Modulation of SK Channel Impedes Neuron-Specific Cytoskeletal Organization and Maturation
Shrestha, A., Sultana, R., Adeniyi, P. A., Lee, C. C., & Ogundele, O. M. (2020) · Developmental Neuroscience · doi:10.1159/000507989 · Cited by 3
Catatonia and genetic variant in GABA receptor: A case report involving GABRB2
Legrand, A., Moyal, M., Deschamps, C., Louveau, C., Iftimovici, A., Krebs, M., Héron, B., Keren, B., Afenjar, A., & Chaumette, B. (2023) · Schizophrenia Research · doi:10.1016/j.schres.2023.07.017 · Cited by 2
Carbonell, A. U., Freire‐Cobo, C., Deyneko, I. V., Erdjument‐Bromage, H., Clipperton‐Allen, A. E., Rasmusson, R. L., Page, D. T., Neubert, T. A., & Jordan, B. A. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.02.02.429412 · Cited by 2
Metadata
- Authors
- Duffney, L. J., Wei, J., Cheng, J., Liu, W., Smith, K. R., Kittler, J. T., & Yan, Z.
- Affiliations
- University College London (GB)
- University at Buffalo, State University of New York (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2013-10-02
- Volume
- 33
- Issue
- 40
- Pages
- 15767-15778
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3787498
- OpenAlex
- W2045491381
- Cited by
- 115
- References
- 87
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 12 · 2021: 14 · 2020: 12 · 2019: 5 · 2018: 11 · 2017: 5 · 2016: 15 · 2015: 13 · 2014: 6
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- National Institutes of Health (5r21mh101690-02, MH-101690)
- National Institute of Mental Health (R21-MH101690, R01MH085774)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Keywords
- SHANK3, NMDA receptor hypofunction, actin cytoskeleton, Rac1, p21-activated kinase, cofilin, glutamatergic synapses, autism spectrum disorder, synaptic currents, cortical neurons, actin depolymerization
- MeSH terms
- Actins, Animals, Cells, Cultured, Cerebral Cortex, Humans, Nerve Tissue Proteins, Synaptic Transmission, Neurons, Synapses, Receptors, N-Methyl-D-Aspartate, rac1 GTP-Binding Protein, RNA Interference, RNA, Small Interfering, Rats, p21-Activated Kinases, HEK293 Cells
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