Synaptic structural protein dysfunction leads to altered excitation inhibition ratios in models of autism spectrum disorder
Abstract
Genetics is believed to play a key role in the development of Autism Spectrum Disorder (ASD) and a plethora of potential candidate genes have been identified by genetic characterization of patients, their family members and controls. To make sense of this information investigators have searched for common pathways and downstream properties of neural networks that are regulated by these genes. For instance, several candidate genes encode synaptic proteins, and one hypothesis that has emerged is that disruption of the synaptic excitation and inhibition (E/I) balance would destabilize neural processing and lead to ASD phenotypes. Some compelling evidence for this has come from the analyses of mouse and culture models with defects in synaptic structural proteins, which influence several aspects of synapse biology and is the subject of this review. Remaining challenges include identifying the specifics that distinguish ASD from other psychiatric diseases and designing more direct tests of the E/I balance hypothesis.
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A shift of the excitation/inhibition balance can result from neurodevelopmental abnormalities targeting inhibitory interneurons or from structural changes at the synapse.
“A shift of the balance can result from neurodevelopmental abnormalities targeting the inhibitory interneurons68 or from structural changes at the synapse69.”
From Elimination of the four extracellular matrix molecules tenascin-C, tenascin-R, brevican and neurocan alters the ratio of excitatory and inhibitory synapses (2019) · cites this paper as [69]
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,841 · see citing works
Diagnostic and Statistical Manual of Mental Disorders
(2012) · Springer eBooks · doi:10.1007/springerreference_121117 · Cited by 20,769 · see citing works
Baio, J., Wiggins, L., Christensen, D. L., Maenner, M. J., Daniels, J., Warren, Z., Kurzius-Spencer, M., Zahorodny, W., Robinson, C., Rosenberg, et al. (2018) · MMWR. Surveillance Summaries · doi:10.15585/mmwr.ss6706a1 · Cited by 6,078 · see citing works
Model of autism: increased ratio of excitation/inhibition in key neural systems
Rubenstein, J. L. R., & Merzenich, M. M. (2003) · Genes, Brain and Behavior · doi:10.1034/j.1601-183x.2003.00037.x · Cited by 2,768 · see citing works
Sporadic autism exomes reveal a highly interconnected protein network of de novo mutations
O’Roak, B. J., Vives, L., Girirajan, S., Karakoc, E., Krumm, N., Coe, B. P., Levy, R., Ko, A., Lee, C., Smith, J. D., et al. (2012) · Nature · doi:10.1038/nature10989 · Cited by 2,165 · see citing works
Functional impact of global rare copy number variation in autism spectrum disorders
Pinto, D., Pagnamenta, A. T., Klei, L., Anney, R., Merico, D., Regan, R., Conroy, J., Magalhaes, T. R., Correia, C., Abrahams, B. S., et al. (2010) · Nature · doi:10.1038/nature09146 · Cited by 2,013 · see citing works
Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism
Study, P. A. R. I. S., Jamain, S., Quach, H., Betancur, C., Råstam, M., Colineaux, C., Gillberg, I. C., Soderstrom, H., Giros, B., Leboyer, M., et al. (2003) · Nature Genetics · doi:10.1038/ng1136 · Cited by 1,851 · see citing works
Shank3 mutant mice display autistic-like behaviours and striatal dysfunction
Peça, J., Feliciano, C., Ting, J. T., Wang, W., Wells, M. F., Venkatraman, T. N., Lascola, C. D., Fu, Z., & Feng, G. (2011) · Nature · doi:10.1038/nature09965 · Cited by 1,570 · see citing works
PDZ domain proteins of synapses
Kim, E., & Sheng, M. (2004) · Nature reviews. Neuroscience · doi:10.1038/nrn1517 · Cited by 1,565 · see citing works
Morphological Changes in Dendritic Spines Associated with Long-Term Synaptic Plasticity
Yuste, R., & Bonhoeffer, T. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1071 · Cited by 1,269 · see citing works
Naisbitt, S., Kim, E., Tu, J. C., Xiao, B., Sala, C., Valtschanoff, J., Weinberg, R. J., Worley, P. F., & Sheng, M. (1999) · Neuron · doi:10.1016/s0896-6273(00)80809-0 · Cited by 1,009 · see citing works
A Neuroligin-3 Mutation Implicated in Autism Increases Inhibitory Synaptic Transmission in Mice
Tabuchi, K., Blundell, J., Etherton, M. R., Hammer, R. E., Liu, X., Powell, C. M., & Südhof, T. C. (2007) · Science · doi:10.1126/science.1146221 · Cited by 997 · see citing works
Postsynaptic clustering of major GABAA receptor subtypes requires the γ2 subunit and gephyrin
Essrich, C., Lorez, M., Benson, J. A., Fritschy, J., & Lüscher, B. (1998) · Nature Neuroscience · doi:10.1038/2798 · Cited by 856 · see citing works
Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice
Welch, J. M., Lu, J., Rodriguiz, R. M., Trotta, N. C., Peca, J., Ding, J.-D., Feliciano, C., Chen, M., Adams, J. P., Luo, J., et al. (2007) · Nature · doi:10.1038/nature06104 · Cited by 852 · see citing works
Structure-stability-function relationships of dendritic spines
Kasai, H., Matsuzaki, M., Noguchi, J., Yasumatsu, N., & Nakahara, H. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00162-0 · Cited by 847 · see citing works
Kirov, G., Pocklington, A. J., Holmans, P., Ivanov, D., Ikeda, M., Ruderfer, D., Moran, J., Chambert, K., Toncheva, D., Georgieva, L., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.154 · Cited by 844 · see citing works
The Cerebellum, Sensitive Periods, and Autism
Wang, S. S. ‐., Kloth, A. D., & Badura, A. (2014) · Neuron · doi:10.1016/j.neuron.2014.07.016 · Cited by 829 · see citing works
Neuroligins Determine Synapse Maturation and Function
Varoqueaux, F., Aramuni, G., Rawson, R. L., Mohrmann, R., Missler, M., Gottmann, K., Zhang, W., Südhof, T. C., & Brose, N. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.003 · Cited by 818 · see citing works
Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits
Südhof, T. C. (2017) · Cell · doi:10.1016/j.cell.2017.10.024 · Cited by 810 · see citing works
The Heritability of Autism Spectrum Disorder
Sandin, S., Lichtenstein, P., Kuja-Halkola, R., Hultman, C., Larsson, H., & Reichenberg, A. (2017) · JAMA · doi:10.1001/jama.2017.12141 · Cited by 776 · see citing works
Regulation of Dendritic Spine Morphology and Synaptic Function by Shank and Homer
Sala, C., Piëch, V., Wilson, N. R., Passafaro, M., Liu, G., & Sheng, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00339-7 · Cited by 716 · see citing works
Control of Excitatory and Inhibitory Synapse Formation by Neuroligins
Chih, B., Engelman, H. S., & Scheiffele, P. (2005) · Science · doi:10.1126/science.1107470 · Cited by 707 · see citing works
α-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis
Missler, M., Zhang, W., Rohlmann, A., Kattenstroth, G., Hammer, R. E., Gottmann, K., & Südhof, T. C. (2003) · Nature · doi:10.1038/nature01755 · Cited by 699 · see citing works
SHANK proteins: roles at the synapse and in autism spectrum disorder
Monteiro, P., & Feng, G. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.183 · Cited by 681 · see citing works
Neurexin–neuroligin signaling in synapse development
Craig, A. M., & Kang, Y. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.01.011 · Cited by 640 · see citing works
Leblond, C. S., Nava, C., Polge, A., Gauthier, J., Huguet, G., Lumbroso, S., Giuliano, F., Stordeur, C., Depienne, C., Mouzat, K., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004580 · Cited by 630 · see citing works
Bozdagi, O., Sakurai, T., Papapetrou, D., Wang, X., Dickstein, D. L., Takahashi, N., Kajiwara, Y., Yang, M., Katz, A. M., Scattoni, M. L., et al. (2010) · Molecular Autism · doi:10.1186/2040-2392-1-15 · Cited by 584 · see citing works
Stessman, H. A. F., Xiong, B., Coe, B. P., Wang, T., Hoekzema, K., Fenckova, M., Kvarnung, M., Gerdts, J., Trinh, S., Cosemans, N., et al. (2017) · Nature Genetics · doi:10.1038/ng.3792 · Cited by 559 · see citing works
Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3
Wang, X., McCoy, P. A., Rodriguiz, R. M., Pan, Y., Je, H. S., Roberts, A. C., Kim, C. J., Berrios, J., Colvin, J. S., Bousquet-Moore, D., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr212 · Cited by 537 · see citing works
Postmortem brain abnormalities of the glutamate neurotransmitter system in autism
Purcell, A. E., Jeon, O. H., Zimmerman, A. W., Blue, M. E., & Pevsner, J. (2001) · Neurology · doi:10.1212/wnl.57.9.1618 · Cited by 518 · see citing works
Kim, E., Naisbitt, S., Hsueh, Y.-P., Rao, A., Rothschild, A., Craig, A. M., & Sheng, M. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.136.3.669 · Cited by 516 · see citing works
Characteristics and Concordance of Autism Spectrum Disorders Among 277 Twin Pairs
Rosenberg, R. E., Law, J. K., Yenokyan, G., McGready, J., Kaufmann, W. E., & Law, P. A. (2009) · Archives of Pediatrics & Adolescent Medicine · doi:10.1001/archpediatrics.2009.98 · Cited by 495 · see citing works
Rothwell, P. E., Fuccillo, M. V., Maxeiner, S., Hayton, S. J., Gokce, O., Lim, B. K., Fowler, S. C., Malenka, R. C., & Südhof, T. C. (2014) · Cell · doi:10.1016/j.cell.2014.04.045 · Cited by 477 · see citing works
Loss of Postsynaptic GABAA Receptor Clustering in Gephyrin-Deficient Mice
Kneussel, M., Brandstätter, J., Laube, B., Stahl, S., Müller, U., & Betz, H. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09289.1999 · Cited by 456 · see citing works
Etherton, M. R., Blaiss, C. A., Powell, C. M., & Südhof, T. C. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0910297106 · Cited by 447 · see citing works
Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity.
Feng, G.-K., Tintrup, H., Kirsch, J., Nichol, M. C., Kuhse, J., Betz, H., & Sanes, J. (1998) · Science · doi:10.1126/science.282.5392.1321 · Cited by 425 · see citing works
Genetics and genomics of psychiatric disease
Geschwind, D. H., & Flint, J. (2015) · Science · doi:10.1126/science.aaa8954 · Cited by 424 · see citing works
Synapse-specific regulation of AMPA receptor function by PSD-95.
Béïque, J.-C., Lin, D.-T., Kang, M.-G., Aizawa, H., Takamiya, K., & Huganir, R. L. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608492103 · Cited by 398 · see citing works
Chih, B., Gollan, L., & Scheiffele, P. (2006) · Neuron · doi:10.1016/j.neuron.2006.06.005 · Cited by 393 · see citing works
Identification of PSD-95 as a Regulator of Dopamine-Mediated Synaptic and Behavioral Plasticity
Yao, W., Gainetdinov, R. R., Arbuckle, M. I., Sotnikova, T. D., Cyr, M., Beaulieu, J., Torres, G. E., Grant, S. G. N., & Caron, M. G. (2004) · Neuron · doi:10.1016/s0896-6273(04)00048-0 · Cited by 380 · see citing works
Neurobehavioral Comorbidities in Children With Active Epilepsy: A Population-Based Study
Reilly, C. J., Atkinson, P., Das, K. B., Chin, R., Aylett, S., Burch, V., Gillberg, C., Scott, R. C., & Neville, B. G. R. (2014) · PEDIATRICS · doi:10.1542/peds.2013-3787 · Cited by 378 · see citing works
Takeuchi, M., Hata, Y., Hirao, K., Toyoda, A., Irie, M., & Takai, Y. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.18.11943 · Cited by 359 · see citing works
Hung, A. Y., Futai, K., Sala, C., Valtschanoff, J. G., Ryu, J., Woodworth, M. A., Kidd, F. L., Sung, C. C., Miyakawa, T., Bear, M. F., et al. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3032-07.2008 · Cited by 350 · see citing works
Synapse Pathology in Psychiatric and Neurologic Disease
van Spronsen, M., & Hoogenraad, C. C. (2010) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-010-0104-8 · Cited by 345 · see citing works
Etherton, M. R., Földy, C., Sharma, M., Tabuchi, K., Liu, X., Shamloo, M., Malenka, R. C., & Südhof, T. C. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111093108 · Cited by 340 · see citing works
Zhou, Y., Kaiser, T., Monteiro, P., Zhang, X., Van der Goes, M. S., Wang, D., Barak, B., Zeng, M., Li, C., Lu, C., et al. (2016) · Neuron · doi:10.1016/j.neuron.2015.11.023 · Cited by 325 · see citing works
Wang, X., Bey, A. L., Katz, B. M., Badea, A., Kim, N., David, L. K., Duffney, L. J., Kumar, S., Mague, S. D., Hulbert, S. W., et al. (2016) · Nature Communications · doi:10.1038/ncomms11459 · Cited by 318 · see citing works
Sensory Integration in Mouse Insular Cortex Reflects GABA Circuit Maturation
Gogolla, N., Takesian, A. E., Feng, G., Fagiolini, M., & Hensch, T. K. (2014) · Neuron · doi:10.1016/j.neuron.2014.06.033 · Cited by 310 · see citing works
Chen, X., Levy, J. M., Hou, A., Winters, C., Azzam, R., Sousa, A. A., Leapman, R. D., Nicoll, R. A., & Reese, T. S. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1517045112 · Cited by 310 · see citing works
Aoto, J. N., Martinelli, D. C., Malenka, R. C., Tabuchi, K., & Südhof, T. C. (2013) · Cell · doi:10.1016/j.cell.2013.05.060 · Cited by 299 · see citing works
Characterization of the Shank Family of Synaptic Proteins
Lim, S., Naisbitt, S., Yoon, J., Hwang, J.-I., Suh, P.-G., Sheng, M., & Kim, E. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.41.29510 · Cited by 295 · see citing works
Hirao, K., Hata, Y., Ide, N., Takeuchi, M., Irie, M., Yao, I., Deguchi, M., Toyoda, A., Südhof, T. C., & Takai, Y. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.33.21105 · Cited by 293 · see citing works
An Architectural Framework That May Lie at the Core of the Postsynaptic Density
Baron, M. K., Boeckers, T. M., Vaida, B., Faham, S., Gingery, M., Sawaya, M. R., Salyer, D., Gundelfinger, E. D., & Bowie, J. U. (2006) · Science · doi:10.1126/science.1118995 · Cited by 292 · see citing works
Sala, C., Futai, K., Yamamoto, K., Worley, P. F., Hayashi, Y., & Sheng, M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06327.2003 · Cited by 288 · see citing works
Truncating mutations in NRXN2 and NRXN1 in autism spectrum disorders and schizophrenia
Gauthier, J., Siddiqui, T. J., Huashan, P., Yokomaku, D., Hamdan, F. F., Champagne, N., Lapointe, M., Spiegelman, D., Noreau, A., Lafrenière, R. G., et al. (2011) · Human Genetics · doi:10.1007/s00439-011-0975-z · Cited by 286 · see citing works
Kouser, M., Speed, H. E., Dewey, C. M., Reimers, J. M., Widman, A. J., Gupta, N., Liu, S., Jaramillo, T. C., Bangash, M. A., Xiao, B., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.3017-13.2013 · Cited by 283 · see citing works
Epilepsy in autism: features and correlates
Bolton, P. F., Carcani-Rathwell, I., Hutton, J., Goode, S., Howlin, P., & Rutter, M. (2011) · British Journal of Psychiatry · doi:10.1192/bjp.bp.109.076877 · Cited by 281 · see citing works
Neuroligins Mediate Excitatory and Inhibitory Synapse Formation
Levinson, J. N., Chéry, N., Huang, K., Wong, T. P., Gerrow, K., Kang, R., Prange, O., Wang, Y. T., & El-Husseini, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m413812200 · Cited by 278 · see citing works
Hussman, J. P. (2001) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1010715619091 · Cited by 263 · see citing works
Naisbitt, S. R., Valtschanoff, J. G., Allison, D. W., Sala, C., Kim, E., Craig, A. M., Weinberg, R. J., & Sheng, M. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-12-04524.2000 · Cited by 259 · see citing works
Cadherins and neuropsychiatric disorders
Redies, C., Hertel, N., & Hübner, C. A. (2012) · Brain Research · doi:10.1016/j.brainres.2012.06.020 · Cited by 257 · see citing works
Lévi, S., Logan, S. M., Tovar, K., & Craig, A. M. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.1661-03.2004 · Cited by 246 · see citing works
Filice, F., Vörckel, K. J., Sungur, A. Ö., Wöhr, M., & Schwaller, B. (2016) · Molecular Brain · doi:10.1186/s13041-016-0192-8 · Cited by 240 · see citing works
Biederer, T., & Südhof, T. C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000656200 · Cited by 240 · see citing works
The emerging role of <i>SHANK</i> genes in neuropsychiatric disorders
Guilmatre, A., Huguet, G., Delorme, R., & Bourgeron, T. (2014) · Developmental Neurobiology · doi:10.1002/dneu.22128 · Cited by 237 · see citing works
Feyder, M. J., Karlsson, R., Mathur, P., Lyman, M., Bock, R., Momenan, R., Munasinghe, J., Scattoni, M. L., Ihne, J. L., Camp, M., et al. (2010) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2010.10040484 · Cited by 233 · see citing works
Paradis, S., Harrar, D. B., Lin, Y., Koon, A. C., Chatterjee, J. H., Griffith, E. C., Zhu, L., Brass, L. F., Chen, C., & Greenberg, M. E. (2007) · Neuron · doi:10.1016/j.neuron.2006.12.012 · Cited by 231 · see citing works
Expression of GABAB Receptors Is Altered in Brains of Subjects with Autism
Fatemi, S. H., Folsom, T. D., Reutiman, T. J., & Thuras, P. D. (2009) · The Cerebellum · doi:10.1007/s12311-008-0075-3 · Cited by 227 · see citing works
Dysfunctional cerebellar Purkinje cells contribute to autism-like behaviour in Shank2-deficient mice
Peter, S., ten Brinke, M. M., Stedehouder, J., Reinelt, C. M., Wu, B., Zhou, H., Zhou, K., Boele, H., Kushner, S. A., Lee, M. G., et al. (2016) · Nature Communications · doi:10.1038/ncomms12627 · Cited by 217 · see citing works
Homer 1b Regulates the Trafficking of Group I Metabotropic Glutamate Receptors
Roche, K. W., Tu, J. C., Petralia, R. S., Xiao, B., Wenthold, R. J., & Worley, P. F. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.36.25953 · Cited by 212 · see citing works
Excitation control: balancing PSD-95 function at the synapse
Keith, D. J. (2008) · Frontiers in Molecular Neuroscience · doi:10.3389/neuro.02.004.2008 · Cited by 206 · see citing works
A Discovery Resource of Rare Copy Number Variations in Individuals with Autism Spectrum Disorder
Prasad, A., Merico, D., Thiruvahindrapuram, B., Wei, J., Lionel, A. C., Sato, D., Rickaby, J., Lu, C., Szatmari, P., Roberts, W., et al. (2012) · G3 Genes|Genomes|Genetics · doi:10.1534/g3.112.004689 · Cited by 206 · see citing works
Exonic Mosaic Mutations Contribute Risk for Autism Spectrum Disorder
Krupp, D. R., Barnard, R. A., Duffourd, Y., Evans, S. A., Mulqueen, R. M., Bernier, R., Rivière, J.-B., Fombonne, E., & O’Roak, B. J. (2017) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.07.016 · Cited by 204 · see citing works
Carlsson, M. L. (1998) · Journal of Neural Transmission · doi:10.1007/s007020050076 · Cited by 186 · see citing works
Szumlinski, K. K., Lominac, K. D., Kleschen, M. J., Oleson, E. B., Dehoff, M. H., Schwartz, M. K., Seeberg, P. H., Worley, P. F., & Kalivas, P. W. (2005) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2005.00120.x · Cited by 181 · see citing works
Blanpied, T. A., & Ehlers, M. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2003.10.006 · Cited by 179 · see citing works
Sergé, A., Fourgeaud, L., Hémar, A., & Choquet, D. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-10-03910.2002 · Cited by 175 · see citing works
PSD-95-like membrane associated guanylate kinases (PSD-MAGUKs) and synaptic plasticity
Xu, W. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.03.001 · Cited by 171 · see citing works
β-Neurexins Control Neural Circuits by Regulating Synaptic Endocannabinoid Signaling
Anderson, G. R., Aoto, J. N., Tabuchi, K., Földy, C., Covy, J. P., Yee, A. X., Wu, D., Lee, S., Chen, L., Malenka, R. C., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.056 · Cited by 166 · see citing works
Dhamne, S. C., Silverman, J. L., Super, C. E., Lammers, S. H. T., Hameed, M. Q., Modi, M. E., Copping, N. A., Pride, M. C., Smith, D. G., Rotenberg, A., et al. (2017) · Molecular Autism · doi:10.1186/s13229-017-0142-z · Cited by 166 · see citing works
Wang, X., Xu, Q., Bey, A. L., Lee, Y., & Jiang, Y. (2014) · Molecular Autism · doi:10.1186/2040-2392-5-30 · Cited by 165 · see citing works
Lionel, A. C., Vaags, A. K., Sato, D., Gazzellone, M. J., Mitchell, E. B., Chen, H. Y., Costain, G., Walker, S., Egger, G., Thiruvahindrapuram, B., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt056 · Cited by 162 · see citing works
Jaramillo, T. C., Speed, H. E., Xuan, Z., Reimers, J. M., Liu, S., & Powell, C. M. (2015) · Autism Research · doi:10.1002/aur.1529 · Cited by 151 · see citing works
Lee, J., Chung, C., Ha, S., Lee, D., Kim, D. Y., Kim, H., & Kim, E. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00094 · Cited by 145 · see citing works
Speed, H. E., Kouser, M., Xuan, Z., Reimers, J. M., Ochoa, C. F., Gupta, N. M., Liu, S., & Powell, C. M. (2015) · Journal of Neuroscience · doi:10.1523/jneurosci.3125-14.2015 · Cited by 138 · see citing works
Integrated systems analysis reveals a molecular network underlying autism spectrum disorders
Li, J., Shi, M., Ma, Z., Zhao, S., Euskirchen, G., Ziskin, J., Urban, A., Hallmayer, J., & Snyder, M. (2014) · Molecular Systems Biology · doi:10.15252/msb.20145487 · Cited by 132 · see citing works
A twin study of heritable and shared environmental contributions to autism
Frazier, T. W., Thompson, L., Youngstrom, E. A., Law, P., Hardan, A. Y., Eng, C., & Morris, N. (2014) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-014-2081-2 · Cited by 120 · see citing works
Kelleher III, R. J., Geigenmüller, U., Hovhannisyan, H., Trautman, E., Pinard, R., Rathmell, B., Carpenter, R., & Margulies, D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035003 · Cited by 116 · see citing works
Genetic influences on the broad spectrum of autism: Study of proband‐ascertained twins
Taniai, H., Nishiyama, T., Miyachi, T., Imaeda, M., & Sumi, S. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30740 · Cited by 110 · see citing works
Ha, S., Lee, D., Cho, Y. S., Chung, C., Yoo, Y.-E., Kim, J., Lee, J., Kim, W., Kim, H., Bae, Y. C., et al. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.1849-16.2016 · Cited by 107 · see citing works
Cellular and synaptic network defects in autism
Peça, J., & Feng, G. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2012.02.015 · Cited by 96 · see citing works
Autism Symptoms in Fragile X Syndrome
Niu, M., Han, Y., Dy, A. B. C., Du, J., Jin, H., Qin, J., Zhang, J., Li, Q., & Hagerman, R. J. (2017) · Journal of Child Neurology · doi:10.1177/0883073817712875 · Cited by 96 · see citing works
Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene
Schoch, H., Kreibich, A. S., Ferri, S. L., White, R. S., Bohorquez, D., Banerjee, A., Port, R. G., Dow, H. C., Cordero, L., Pallathra, A. A., et al. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.06.008 · Cited by 92 · see citing works
Deletion of α-neurexin II results in autism-related behaviors in mice
Dachtler, J., Glasper, J., Cohen, R. N., Ivorra, J. L., Swiffen, D. J., Jackson, A. J., Harte, M. K., Rodgers, R. J., & Clapcote, S. J. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.123 · Cited by 84 · see citing works
The role of cadherin genes in five major psychiatric disorders: A literature update
Hawi, Z., Tong, J., Dark, C., Yates, H., Johnson, B. P., & Bellgrove, M. A. (2017) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32592 · Cited by 78 · see citing works
Gazzellone, M. J., Zarrei, M., Burton, C. L., Walker, S., Uddin, M., Shaheen, S. M., Coste, J., Rajendram, R., Schachter, R. J., Colasanto, M., et al. (2016) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-016-9170-9 · Cited by 77 · see citing works
Cadherins Interact With Synaptic Organizers to Promote Synaptic Differentiation
Yamagata, M., Duan, X., & Sanes, J. R. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00142 · Cited by 77 · see citing works
Herweg, J., & Schwarz, G. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.341826 · Cited by 75 · see citing works
Schwabe, T., Neuert, H., & Clandinin, T. R. (2013) · Cell · doi:10.1016/j.cell.2013.06.011 · Cited by 72 · see citing works
Deficiency of Shank2 causes mania-like behavior that responds to mood stabilizers
Pappas, A. L., Bey, A. L., Wang, X., Rossi, M. A., Kim, Y. H., Yan, H., Porkka, F., Duffney, L. J., Phillips, S. M., Cao, X., et al. (2017) · JCI Insight · doi:10.1172/jci.insight.92052 · Cited by 70 · see citing works
Xing, J., Kimura, H., Wang, C., Ishizuka, K., Kushima, I., Arioka, Y., Yoshimi, A., Nakamura, Y., Shiino, T., Oya‐Ito, T., et al. (2016) · Scientific Reports · doi:10.1038/srep27491 · Cited by 68 · see citing works
Zhu, J., Zhou, Q., Shang, Y., Li, H., Peng, M., Ke, X., Weng, Z., Zhang, R., Huang, X., Li, S. S. C., et al. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.11.107 · Cited by 68 · see citing works
Functional Heterogeneity of Gephyrins
Meier, J. C., de Chaldée, M., Triller, A., & Vannier, C. (2000) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0899 · Cited by 65 · see citing works
Postsynaptic scaffolding molecules modulate the localization of neuroligins
Levinson, J. N., Li, R.-X., Kang, R., Moukhles, H., El-Husseini, A., & Bamji, S. X. (2009) · Neuroscience · doi:10.1016/j.neuroscience.2009.11.016 · Cited by 53 · see citing works
Scaffolding protein Homer1a protects against NMDA-induced neuronal injury
Wang, Y., Rao, W., Zhang, C., Zhang, C., Liu, M.-D., Han, F., Yao, L.-B., Han, H., Luo, P., Su, N., et al. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.216 · Cited by 50 · see citing works
Cai, C., Li, H., Rivera, C., & KEINÄNEN, K. P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505886200 · Cited by 50 · see citing works
Effects of N-cadherin disruption on spine morphological dynamics
Mysore, S. P. (2007) · Frontiers in Cellular Neuroscience · doi:10.3389/neuro.03.001.2007 · Cited by 50 · see citing works
Coba, M. P., Ramaker, M. J., Ho, E. V., Thompson, S. L., Komiyama, N. H., Grant, S. G. N., Knowles, J. A., & Dulawa, S. C. (2018) · Scientific Reports · doi:10.1038/s41598-018-20610-y · Cited by 48 · see citing works
Banerjee, A., Luong, J. A., Ho, A., Saib, A., & Ploski, J. E. (2016) · Molecular Autism · doi:10.1186/s13229-016-0077-9 · Cited by 43 · see citing works
Zhang, B., Gökçe, Ö., Hale, W. D., Brose, N., & Südhof, T. C. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20172162 · Cited by 41 · see citing works
Yuan, H., Wang, Q., Liu, Y., Yang, W., He, Y., Gusella, J. F., Song, J., & Shen, Y. (2018) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32673 · Cited by 30 · see citing works
Expression and subcellular distribution of gephyrin in non-neuronal tissues and cells
Nawrotzki, R., Islinger, M., Vogel, I., Völkl, A., & Kirsch, J. (2012) · Histochemistry and Cell Biology · doi:10.1007/s00418-012-0914-7 · Cited by 29 · see citing works
Cadherin-10 Maintains Excitatory/Inhibitory Ratio through Interactions with Synaptic Proteins
Smith, K. R., Jones, K. A., Kopeikina, K. J., Burette, A. C., Copits, B. A., Yoon, S., Forrest, M. P., Fawcett‐Patel, J. M., Hanley, J. G., Weinberg, R. J., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.1153-17.2017 · Cited by 29 · see citing works
Self-citationConditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors
Tantra, M., Guo, L., Kim, J., Zainolabidin, N., Eulenburg, V., Augustine, G. J., & Chen, A. I. (2018) · Genes Brain & Behavior · doi:10.1111/gbb.12466 · Cited by 23 · see citing works
Poquet, H., Faivre, L. O., Chehadeh, S. E., Morton, J. E. V., McMullan, D. J., Hamilton, S., Goel, H., Isidor, B., Caignec, C. L., Andrieux, J., et al. (2017) · Autism - Open Access · doi:10.4172/2165-7890.1000197 · Cited by 9 · see citing works
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7 of the 122 references couldn’t be matched to a known paper.
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Gottschling, C., Wegrzyn, D., Denecke, B., & Faissner, A. (2019) · Scientific Reports · doi:10.1038/s41598-019-50404-9 · Cited by 111 · see citing works
Alterations in GABAA-Receptor Trafficking and Synaptic Dysfunction in Brain Disorders
Mele, M., Costa, R. O., & Duarte, C. B. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00077 · Cited by 106 · see citing works
Culotta, L., & Penzes, P. (2020) · Molecular Autism · doi:10.1186/s13229-020-00339-0 · Cited by 77 · see citing works
Gąssowska-Dobrowolska, M., Cieślik, M., Czapski, G. A., Jęśko, H. M., Frontczak‐Baniewicz, M., Gewartowska, M., Dominiak, A., Polowy, R., Filipkowski, R. K., Babiec, L., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21103576 · Cited by 75 · see citing works
Bartolomeo, M. D., Štark, T., Maurel, O. M., Iannotti, F. A., Kuchař, M., Kučerová, J., Piscitelli, F., Laudani, S., Pekařík, V., Salomone, S., et al. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.105357 · Cited by 76 · see citing works
Excitation/Inhibition Modulators in Autism Spectrum Disorder: Current Clinical Research
Canitano, R., & Palumbi, R. (2021) · Frontiers in Neuroscience · doi:10.3389/fnins.2021.753274 · Cited by 60 · see citing works
Gąssowska-Dobrowolska, M., Kolasa, A., Cieślik, M., Dominiak, A., Friedland, K., & Adamczyk, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22063209 · Cited by 45 · see citing works
Cytokine Signalling at the Microglial Penta-Partite Synapse
Aramideh, J. A., Vidal-Itriago, A., Morsch, M., & Graeber, M. B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413186 · Cited by 35 · see citing works
Šimić, G., Vukić, V., Kopić, J., Krsnik, Ž., & Hof, P. R. (2020) · Biomolecules · doi:10.3390/biom11010002 · Cited by 25 · see citing works
Luo, L., Chen, J., Wu, Q., Yuan, B., Hu, C., Yang, T., Wei, H., & Li, T. (2023) · Environmental Toxicology and Pharmacology · doi:10.1016/j.etap.2023.104090 · Cited by 24 · see citing works
Wang, M., Liu, X., Hou, Y., Zhang, H., Kang, J., Wang, F., Zhao, Y., Chen, J., Liu, X., Wang, Y., et al. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00447 · Cited by 22 · see citing works
mTOR-Dependent Spine Dynamics in Autism
Chaudry, S., & Vasudevan, N. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.877609 · Cited by 22 · see citing works
Di, Y., Li, Z., Li, J., Cheng, Q., Zheng, Q., Zhai, C., Kang, M., Wei, C., Lan, J., Fan, J., et al. (2021) · Food & Function · doi:10.1039/d0fo02926b · Cited by 17 · see citing works
A high‐salt diet induces synaptic loss and memory impairment via gut microbiota and butyrate in mice
Lei, C., Liu, C., Peng, Y., Zhan, Y., Zhang, X., Liu, T., & Liu, Z. (2023) · iMeta · doi:10.1002/imt2.97 · Cited by 15 · see citing works
Imbalanced Gamma-band Functional Brain Networks of Autism Spectrum Disorders
Wang, C., Feng, C., Zhou, Z., Cao, W.-Y., Danjun, H., Jiang, Z., & Lin, F. (2022) · Neuroscience · doi:10.1016/j.neuroscience.2022.01.021 · Cited by 14 · see citing works
González-Madrid, E., Rangel-Ramírez, M. A., Opazo, M. C., Méndez, L., Böhmwald, K., Bueno, S. M., González, P. A., Kalergis, A. M., & Riedel, C. A. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1381180 · Cited by 14 · see citing works
Gąssowska-Dobrowolska, M., Kolasa, A., Beversdorf, D. Q., & Adamczyk, A. (2022) · Biomedicines · doi:10.3390/biomedicines10123031 · Cited by 13 · see citing works
D’Antoni, S., Schiavi, S., Buzzelli, V., Giuffrida, S., Feo, A., Ascone, F., Busceti, C. L., Nicoletti, F., Trezza, V., & Catania, M. V. (2023) · Psychopharmacology · doi:10.1007/s00213-023-06457-w · Cited by 12 · see citing works
Cortical development dynamics across autism spectrum disorder mouse models
Schwarz, L. A., Dotter, C. P., Isaev, S. V., Lisi, M., Malzl, D., Bueschl, C., Ladstätter, S., Oliveira, B., Barel, M., Basilico, B., et al. (2026) · Nature · doi:10.1038/s41586-026-10679-1 · Cited by 10 · see citing works
Shillington, A., Lamy, M., Vawter‐Lee, M., Erickson, C. A., Saal, H. M., Comoletti, D., & Abell, K. B. (2020) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-020-04531-2 · Cited by 7 · see citing works
Rajagopal, L., Huang, M., He, W., Ryan, C., Elzokaky, A., Banerjee, P., & Meltzer, H. Y. (2022) · SSRN Electronic Journal · doi:10.2139/ssrn.4042881 · Cited by 5 · see citing works
Les modèles animaux d’étude de l’autisme: Le modèle « valproate »
Bossu, J. L., & Roux, S. (2019) · HAL · doi:10.1051/medsci/2019036 · Cited by 4 · see citing works
Palollathil, A., Mahin, A., Gopalakrishnan, A. P., Poojari, T. R., Sambreena, A., Shivamurthy, P. B., & Raju, R. (2026) · Proteomes · doi:10.3390/proteomes14010008 · Cited by 3 · see citing works
Soylu, A., Alim, E., Dizakar, S. Ö. A., Atalar, K., & Bahçelioğlu, M. (2025) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.1007/s44411-025-00098-5 · Cited by 3 · see citing works
Hinckelmann, M.-V., Dubos, A., Artot, V., Rudolf, G., Nguyen, T. L., Tilly, P., Nalesso, V., Moreno, M. D. M. M., Birling, M., Godin, J. D., et al. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03109-7 · Cited by 4 · see citing works
Hinckelmann, M.-V., Dubos, A., Artot, V., Rudolf, G., Nguyen, T. L., Tilly, P., Nalesso, V., Moreno, M. D. M. M., Birling, M., Godin, J. D., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.11.09.566424 · Cited by 2 · see citing works
Serotonin 5‐ HT 7 receptor signaling in neuropsychiatric disorders
Park, E., & Choo, H. (2026) · Bulletin of the Korean Chemical Society · doi:10.1002/bkcs.70172 · Cited by 1 · see citing works
Mechanisms Underlying Maintenance of Adult Visual Receptive Fields
Mudd, D. B. (2022) · Digital Archive @ GSU · doi:10.57709/14967304
González-Madrid, E., Rangel-Ramírez, M. A., Opazo, M. C., Méndez, L., Bueno, S. M., González, P. A., Kalergis, A. M., & Riedel, C. A. (2023) · Research Square · doi:10.21203/rs.3.rs-3410622/v1
Yin, H., Sun, K., Wang, C., Fan, S., Wang, J., He, S., Lei, H. M., Pang, S., Chen, J., & Zhang, G. G. (2026) · Molecular Brain · doi:10.1186/s13041-026-01289-z
Beta power as a neural correlate of sensory features in autistic individuals
Chaudet, J., Pichot, J., Pedoux, A., Fleury, M., Maruani, A., Vantalon, V., Humeau, É., Bourgeron, T., Houenou, J., Dumas, G., et al. (2026) · Journal of Neurodevelopmental Disorders · doi:10.1186/s11689-026-09685-1
Bertoni, A. (2019) · theses.fr (ABES) · doi:10.70675/d43fcf44zc66ez47a1zae43zd20439e2b233
d’Albis, M.-A. (2020) · theses.fr (ABES) · doi:10.70675/206f79f9z2fd3z499fz9abdz096c72713a99
Osredkar, J., Godnov, U., Vrhovšek, M. J., Osredkar, D., Avguštin, G., Štiglic, A. F., Fabjan, T., & Kumer, K. (2026) · Scientific Reports · doi:10.21203/rs.3.rs-9433871/v1
- Authors
- Howell, B. W., & Smith, K. M.
- Affiliations
- SUNY Upstate Medical University (US)
- Corresponding author
- Howell, Brian W.
- ORCID
- Howell, Brian W.
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2019-01
- Volume
- 139
- Pages
- 207-214
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W2901950380
- Semantic Scholar
- a056a13ce555d5bc6aa7525b735f758e889c220a
- Cited by
- 35
- References
- 122
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 1 · 2023: 5 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 6
- FWCI
- 0.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- autism spectrum disorder, excitation-inhibition balance, synaptic dysfunction, candidate genes, mouse model, cultural models, neural network stability
- MeSH terms
- Autism Spectrum Disorder, Animals, Humans, Membrane Proteins, Synapses, Intracellular Signaling Peptides and Proteins
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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.
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