Autistic-like behaviour in Scn1a+/− mice and rescue by enhanced GABA-mediated neurotransmission
Open accessAbstract
Haploinsufficiency of the SCN1A gene encoding voltage-gated sodium channel Na(V)1.1 causes Dravet's syndrome, a childhood neuropsychiatric disorder including recurrent intractable seizures, cognitive deficit and autism-spectrum behaviours. The neural mechanisms responsible for cognitive deficit and autism-spectrum behaviours in Dravet's syndrome are poorly understood. Here we report that mice with Scn1a haploinsufficiency exhibit hyperactivity, stereotyped behaviours, social interaction deficits and impaired context-dependent spatial memory. Olfactory sensitivity is retained, but novel food odours and social odours are aversive to Scn1a(+/-) mice. GABAergic neurotransmission is specifically impaired by this mutation, and selective deletion of Na(V)1.1 channels in forebrain interneurons is sufficient to cause these behavioural and cognitive impairments. Remarkably, treatment with low-dose clonazepam, a positive allosteric modulator of GABA(A) receptors, completely rescued the abnormal social behaviours and deficits in fear memory in the mouse model of Dravet's syndrome, demonstrating that they are caused by impaired GABAergic neurotransmission and not by neuronal damage from recurrent seizures. These results demonstrate a critical role for Na(V)1.1 channels in neuropsychiatric functions and provide a potential therapeutic strategy for cognitive deficit and autism-spectrum behaviours in Dravet's syndrome.
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?
Loss-of-function variants of NaV1.1 cause Dravet syndrome and generalized epilepsy with febrile seizures plus, and have also been associated with ASD.
“Loss of function variants of NaV1.1 cause Dravet syndrome [48], generalized epilepsy with febrile seizures plus [49], and have also been associated with ASD [50,51].”
From Progress in Understanding and Treating SCN2A-Mediated Disorders (2018) · cites this paper as [51]
Low doses of clonazepam completely rescued abnormal social behaviors and fear-memory deficits in Scn1a+/- mice.
“Low doses of clonazepam completely rescued the abnormal social behaviors and deficits in fear memory typically presented by Scn1a+/- mice (Han et al., 2012), demonstrating the impact of restoring the proper coordination of inhibitory transmissions.”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Han et al., 2012
Restoring proper coordination of inhibitory transmission can rescue behavioral abnormalities in a Scn1a+/- mouse model.
“Low doses of clonazepam completely rescued the abnormal social behaviors and deficits in fear memory typically presented by Scn1a+/- mice (Han et al., 2012), demonstrating the impact of restoring the proper coordination of inhibitory transmissions.”
From Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops (2016) · cites this paper as Han et al., 2012
In mice haploinsufficient for Scn1a, treatment with low-dose clonazepam completely reversed abnormal social behaviors and deficits in fear memory.
“In mice haploinsufficient for Scn1a , treatment with low-dose clonazepam, a positive allosteric modulator of GABAA receptors, completely reversed the abnormal social behaviors and deficits in fear memory 77 .”
From Progress toward treatments for synaptic defects in autism (2013) · cites this paper as [77]
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
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
Self-citationNeocortical excitation/inhibition balance in information processing and social dysfunction
Yizhar, O., Fenno, L. E., Prigge, M., Schneider, F., Davidson, T. J., O’Shea, D. J., Sohal, V. S., Goshen, I., Finkelstein, J., Paz, J. T., et al. (2011) · Nature · doi:10.1038/nature10360 · Cited by 2,454 · 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
From Ionic Currents to Molecular Mechanisms
Catterall, W. A. (2000) · Neuron · doi:10.1016/s0896-6273(00)81133-2 · Cited by 2,124 · see citing works
Self-citationAdvances in autism genetics: on the threshold of a new neurobiology
Abrahams, B. S., & Geschwind, D. H. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2346 · Cited by 1,866 · see citing works
Paraganglioma of the filum terminale internum
Kamalian, N., Abbassioun, K., Amirjamshidi, A., & Shams-Shahrabadi, M. (1987) · Journal of Neurology · doi:10.1007/bf00314201 · Cited by 1,595 · see citing works
Report of a case and review of the literature
Kamalian, N., Abbassioun, K., Amirjamshidi, A., et al. (1987) · Cited by 1,576 · see citing works
Behavioural phenotyping assays for mouse models of autism
Silverman, J. L., Yang, M., Lord, C., & Crawley, J. N. (2010) · Nature Reviews Neuroscience · doi:10.1038/nrn2851 · Cited by 1,462 · see citing works
De Novo Mutations in the Sodium-Channel Gene SCN1A Cause Severe Myoclonic Epilepsy of Infancy
Claes, L., Del-Favero, J., Ceulemans, B., Lagae, L., Van Broeckhoven, C., & De Jonghe, P. (2001) · The American Journal of Human Genetics · doi:10.1086/320609 · Cited by 1,292 · see citing works
Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations
O'Roak, B. J., Deriziotis, P., Lee, C., Vives, L., Schwartz, J. J., Girirajan, S., Karakoc, E., MacKenzie, A. P., Ng, S. B., Baker, C., et al. (2011) · Nature Genetics · doi:10.1038/ng.835 · Cited by 1,203 · see citing works
Yu, F. H., Mantegazza, M., Westenbroek, R. E., Robbins, C. A., Kalume, F., Burton, K. A., Spain, W. J., McKnight, G. S., Scheuer, T., & Catterall, W. A. (2006) · Nature Neuroscience · doi:10.1038/nn1754 · Cited by 1,173 · see citing works
Self-citationDysfunction in GABA signalling mediates autism-like stereotypies and Rett syndrome phenotypes
Chao, H.-T., Chen, H., Samaco, R. C., Xue, M., Chahrour, M., Yoo, J., Neul, J. L., Gong, S., Lu, H.-C., Heintz, N., et al. (2010) · Nature · doi:10.1038/nature09582 · Cited by 1,168 · see citing works
Self-citationPeñagarikano, O., Abrahams, B. S., Herman, E. I., Winden, K. D., Gdalyahu, A., Dong, H., Sonnenblick, L. I., Gruver, R., Almajano, J., Bragin, A., et al. (2011) · Cell · doi:10.1016/j.cell.2011.08.040 · Cited by 1,075 · see citing works
Molecular and neuronal substrate for the selective attenuation of anxiety
Löw, K., Crestani, F., Keist, R., Benke, D., Brünig, I., Benson, J. A., Fritschy, J.-M., Rülicke, T., Bluethmann, H., Möhler, H., et al. (2000) · Science · doi:10.1126/science.290.5489.131 · Cited by 946 · see citing works
Ogiwara, I., Miyamoto, H., Morita, N., Atapour, N., Mazaki, E., Inoue, I., Takeuchi, T., Itohara, S., Yanagawa, Y., Obata, K., et al. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.5270-06.2007 · Cited by 879 · see citing works
Beyond classical benzodiazepines: novel therapeutic potential of GABAA receptor subtypes
Rudolph, U., & Knoflach, F. (2011) · Nature Reviews Drug Discovery · doi:10.1038/nrd3502 · Cited by 733 · see citing works
Genetics of autism spectrum disorders
Geschwind, D. H. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.07.003 · Cited by 696 · see citing works
The Intense World Theory – A Unifying Theory of the Neurobiology of Autism
Markram, H., & Markram, H. (2010) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2010.00224 · Cited by 522 · see citing works
Differential subcellular localization of the RI and RII Na+ channel subtypes in central neurons
Westenbroek, R. E., Merrick, D., & Catterall, W. A. (1989) · Neuron · doi:10.1016/0896-6273(89)90238-9 · Cited by 477 · see citing works
Self-citationNa<sub>V</sub>1.1 channels and epilepsy
Catterall, W. A., Kalume, F., & Oakley, J. C. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.187484 · Cited by 428 · see citing works
Self-citationStructure and function of voltage‐gated sodium channels
Marbán, E., Yamagishi, T., & Tomaselli, G. F. (1998) · The Journal of Physiology · doi:10.1111/j.1469-7793.1998.647bp.x · Cited by 362 · see citing works
Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome
Moretti, P. M., Bouwknecht, J. A., Teague, R. M., Paylor, R. E., & Zoghbi, H. Y. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddi016 · Cited by 343 · see citing works
Cheah, C. S., Yu, F. H., Westenbroek, R. E., Kalume, F. K., Oakley, J. C., Potter, G. B., Rubenstein, J. L., & Catterall, W. A. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211591109 · Cited by 336 · see citing works
Self-citationWolff, M., Cassé‐Perrot, C., & Dravet, C. (2006) · Epilepsia · doi:10.1111/j.1528-1167.2006.00688.x · Cited by 308 · see citing works
Sodium channels SCN1A, SCN2A and SCN3A in familial autism
Weiss, L. A., Escayg, A., Kearney, J. A., Trudeau, M., MacDonald, B. T., Mori, M., Reichert, J. G., Buxbaum, J. D., & Meisler, M. H. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001241 · Cited by 294 · see citing works
Dravet syndrome: The long‐term outcome
Genton, P., Velizarova, R., & Dravet, C. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03001.x · Cited by 266 · see citing works
Hussman, J. P. (2001) · Journal of Autism and Developmental Disorders · doi:10.1023/a:1010715619091 · Cited by 263 · see citing works
Kalume, F. K., Yu, F. H., Westenbroek, R. E., Scheuer, T., & Catterall, W. A. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2162-07.2007 · Cited by 260 · see citing works
Self-citationTemperature- and age-dependent seizures in a mouse model of severe myoclonic epilepsy in infancy
Oakley, J. C., Kalume, F. K., Yu, F. H., Scheuer, T., & Catterall, W. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0813330106 · Cited by 239 · see citing works
Self-citationPolarized distribution of ion channels within microdomains of the axon initial segment
Wart, A. V., Trimmer, J. S., & Matthews, G. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.21173 · Cited by 222 · see citing works
Change detection in children with autism: an auditory event-related fMRI study
Gomot, M., Bernard, F. A., Davis, M. H., Belmonte, M. K., Ashwin, C., Bullmore, E. T., & Baron-Cohen, S. (2006) · NeuroImage · doi:10.1016/j.neuroimage.2005.07.027 · Cited by 199 · see citing works
Genetics and Function of Neocortical GABAergic Interneurons in Neurodevelopmental Disorders
Rossignol, E. (2011) · Neural Plasticity · doi:10.1155/2011/649325 · Cited by 183 · see citing works
Long, J. E., Cobos, I., Potter, G. B., & Rubenstein, J. L. R. (2009) · Cerebral Cortex · doi:10.1093/cercor/bhp045 · Cited by 178 · see citing works
Self-citationFragile X Syndrome: The GABAergic System and Circuit Dysfunction
Paluszkiewicz, S. M., Martin, B. S., & Huntsman, M. M. (2011) · Developmental Neuroscience · doi:10.1159/000329420 · Cited by 177 · see citing works
Wang, Z., Sindreu, C. B., Li, V., Nudelman, A. S., Chan, G. C. ‐., & Storm, D. R. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.1967-06.2006 · Cited by 138 · see citing works
Comorbidities and predictors of health‐related quality of life in Dravet syndrome
Brunklaus, A., Dorris, L., & Zuberi, S. M. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03129.x · Cited by 123 · see citing works
Behavioral aspects of pediatric epilepsy syndromes
Besag, F. (2003) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2003.11.002 · Cited by 123 · see citing works
Potter, G. B., Petryniak, M. A., Shevchenko, E., McKinsey, G. L., Ekker, M., & Rubenstein, J. L. R. (2008) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2008.10.003 · Cited by 122 · see citing works
Self-citationLi, B.-M., Liu, X., Yi, Y., Deng, Y., Su, T., Zou, X., & Liao, W. (2011) · Epilepsy & Behavior · doi:10.1016/j.yebeh.2011.04.060 · 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
Impaired inhibitory control of cortical synchronization in fragile X syndrome
Paluszkiewicz, S. M., Olmos-Serrano, J. L., Corbin, J. G., & Huntsman, M. M. (2011) · Journal of Neurophysiology · doi:10.1152/jn.00421.2011 · Cited by 107 · see citing works
Olfactory perception, communication, and the nose-to-brain pathway
Stockhorst, U., & Pietrowsky, R. (2004) · Physiology & Behavior · doi:10.1016/j.physbeh.2004.07.018 · Cited by 100 · see citing works
Early diagnosis of severe myoclonic epilepsy in infancy
Yakoub, M., Dulac, O., Jambaqué, I., Chiron, C., & Plouin, P. (1992) · Brain and Development · doi:10.1016/s0387-7604(12)80147-1 · Cited by 99 · see citing works
Han, S., Yu, F. H., Schwartz, M. D., Linton, J. D., Bosma, M. M., Hurley, J. B., Catterall, W. A., & de la Iglesia, H. O. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1115729109 · Cited by 97 · see citing works
Self-citation2q24–q31 Deletion: Report of a case and review of the literature
Pescucci, C., Caselli, R., Grosso, S., Mencarelli, M. A., Mari, F., Farnetani, M. A., Piccini, B., Artuso, R., Bruttini, M., Priolo, M., et al. (2006) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2006.09.001 · Cited by 87 · see citing works
Olfactory perception, communication, and the nose-to-brain pathway
Stockhorst, U., & Pietrowsky, R. (2004) · Physiology & Behavior · doi:10.1016/s0031-9384(04)00343-9 · Cited by 68 · see citing works
Ramoz, N., Cai, G., Reichert, J. G., Silverman, J. M., & Buxbaum, J. D. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30739 · Cited by 55 · see citing works
Variable neurologic phenotype in a GEFS+ family with a novel mutation in SCN1A
Mahoney, K., Moore, S., Buckley, D. J., Alam, M. A., Parfrey, P. S., Penney, S., Merner, N. D., Hodgkinson, K. A., & Young, T. (2009) · Seizure · doi:10.1016/j.seizure.2009.04.009 · Cited by 34 · see citing works
Marneros, A., & Pillmann, F. (2004) · Cambridge University Press eBooks · doi:10.1017/cbo9780511544002.009 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders
Mariani, J., Coppola, G., Zhang, P., Abyzov, A., Provini, L., Tomasini, L., Amenduni, M., Szekely, A., Palejev, D., Wilson, M., et al. (2015) · Cell · doi:10.1016/j.cell.2015.06.034 · Cited by 1,149 · see citing works
Network abnormalities and interneuron dysfunction in Alzheimer disease
Palop, J. J., & Mucke, L. (2016) · Nature reviews. Neuroscience · doi:10.1038/nrn.2016.141 · Cited by 1,022 · see citing works
Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders
Nelson, S. B., & Valakh, V. (2015) · Neuron · doi:10.1016/j.neuron.2015.07.033 · Cited by 1,001 · see citing works
Sohal, V. S., & Rubenstein, J. L. R. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0426-0 · Cited by 988 · see citing works
Self-citationAdvancing the understanding of autism disease mechanisms through genetics
de la Torre-Ubieta, L., Won, H., Stein, J. L., & Geschwind, D. H. (2016) · Nature Medicine · doi:10.1038/nm.4071 · Cited by 827 · see citing works
Ferguson, B. R., & Gao, W.-J. (2018) · Frontiers in Neural Circuits · doi:10.3389/fncir.2018.00037 · Cited by 594 · 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
Costa, L. G., Cole, T. B., Dao, K., Chang, Y. C., Coburn, J. L., & Garrick, J. M. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107523 · Cited by 490 · see citing works
Jiang, Y.-H., Yuen, R. K. C., Jin, X., Wang, M., Chen, N., Wu, X., Ju, J., Mei, J., Shi, Y., He, M., et al. (2013) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2013.06.012 · Cited by 474 · see citing works
Excitation/Inhibition Imbalance in Animal Models of Autism Spectrum Disorders
Lee, E., Lee, J., & Kim, E. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.011 · Cited by 468 · see citing works
Elucidating an Affective Pain Circuit that Creates a Threat Memory
Han, S., Soleiman, M. T., Soden, M. E., Zweifel, L. S., & Palmiter, R. D. (2015) · Cell · doi:10.1016/j.cell.2015.05.057 · Cited by 447 · see citing works
Self-citationBaraban, S. C., Dinday, M. T., & Hortopan, G. A. (2013) · Nature Communications · doi:10.1038/ncomms3410 · Cited by 432 · see citing works
Antoine, M. W., Langberg, T., Schnepel, P., & Feldman, D. E. (2019) · Neuron · doi:10.1016/j.neuron.2018.12.026 · Cited by 413 · see citing works
Cannabidiol attenuates seizures and social deficits in a mouse model of Dravet syndrome
Kaplan, J. S., Stella, N., Catterall, W. A., & Westenbroek, R. E. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1711351114 · Cited by 379 · see citing works
Self-citationCHD8 haploinsufficiency results in autistic-like phenotypes in mice
Katayama, Y., Nishiyama, M., Shoji, H., Ohkawa, Y., Kawamura, A., Sato, T., Suyama, M., Takumi, T., Miyakawa, T., & Nakayama, K. I. (2016) · Nature · doi:10.1038/nature19357 · Cited by 353 · see citing works
Progress in Understanding and Treating SCN2A-Mediated Disorders
Sanders, S. J., Campbell, A. J., Cottrell, J. R., Moller, R. S., Wagner, F. F., Auldridge, A. L., Bernier, R. A., Catterall, W. A., Chung, W. K., Empfield, J. R., et al. (2018) · Trends in Neurosciences · doi:10.1016/j.tins.2018.03.011 · Cited by 338 · see citing works
Self-citationCho, K. K. A., Hoch, R., Lee, A. T., Patel, T., Rubenstein, J. L. R., & Sohal, V. S. (2015) · Neuron · doi:10.1016/j.neuron.2015.02.019 · Cited by 329 · see citing works
Self-citationSelimbeyoglu, A., Kim, C. K., Inoue, M., Lee, S. Y., Hong, A. S. O., Kauvar, I., Ramakrishnan, C., Fenno, L. E., Davidson, T. J., Wright, M., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah6733 · Cited by 326 · see citing works
Rudolph, U., & Möhler, H. (2014) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011613-135947 · Cited by 319 · 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
GABAergic Signaling as Therapeutic Target for Autism Spectrum Disorders
Cellot, G., & Cherubini, E. (2014) · Frontiers in Pediatrics · doi:10.3389/fped.2014.00070 · Cited by 301 · see citing works
GABA progenitors grafted into the adult epileptic brain control seizures and abnormal behavior
Hunt, R. F., Girskis, K. M., Rubenstein, J. L. R., Álvarez-Buylla, A., & Baraban, S. C. (2013) · Nature Neuroscience · doi:10.1038/nn.3392 · Cited by 300 · see citing works
Self-citationThe GABAA Receptor as a Therapeutic Target for Neurodevelopmental Disorders
Braat, S., & Kooy, R. F. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.042 · Cited by 294 · see citing works
Masini, E., Loi, E., Vega-Benedetti, A. F., Carta, M., Doneddu, G., Fadda, R., & Zavattari, P. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218290 · Cited by 293 · see citing works
Selective spider toxins reveal a role for the Nav1.1 channel in mechanical pain
Osteen, J. D., Herzig, V., Gilchrist, J. M., Emrick, J. J., Zhang, C., Wang, X., Castro, J., Garcia‐Caraballo, S., Grundy, L., Rychkov, G. Y., et al. (2016) · Nature · doi:10.1038/nature17976 · Cited by 286 · see citing works
Lessons learned from studying syndromic autism spectrum disorders
Sztainberg, Y., & Zoghbi, H. Y. (2016) · Nature Neuroscience · doi:10.1038/nn.4420 · Cited by 286 · see citing works
Wang, X., Wang, B., Wu, C., Wang, J., & Sun, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24031819 · Cited by 274 · see citing works
Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications
Jiang, C.-C., Lin, L., Long, S., Ke, X., Fukunaga, K., Lu, Y., & Han, F. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01081-0 · Cited by 272 · see citing works
Deidda, G., Parrini, M., Naskar, S., Bozarth, I. F., Contestabile, A., & Cancedda, L. (2015) · Nature Medicine · doi:10.1038/nm.3827 · Cited by 268 · see citing works
Tai, C., Abe, Y., Westenbroek, R. E., Scheuer, T., & Catterall, W. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1411131111 · Cited by 266 · see citing works
Self-citationAnimal models in epilepsy research: legacies and new directions
Grone, B. P., & Baraban, S. C. (2015) · Nature Neuroscience · doi:10.1038/nn.3934 · Cited by 258 · see citing works
The Emerging Picture of Autism Spectrum Disorder: Genetics and Pathology
Chen, J. A., Peñagarikano, O., Belgard, T. G., Swarup, V., & Geschwind, D. H. (2015) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-012414-040405 · Cited by 254 · see citing works
Neurobiological bases of autism–epilepsy comorbidity: a focus on excitation/inhibition imbalance
Bozzi, Y., Provenzano, G., & Casarosa, S. (2018) · European Journal of Neuroscience · doi:10.1111/ejn.13595 · Cited by 250 · see citing works
Pribiag, H., & Stellwagen, D. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.0530-13.2013 · Cited by 249 · see citing works
Modeling non-syndromic autism and the impact of TRPC6 disruption in human neurons
Griesi-Oliveira, K., Acab, A., Gupta, A. R., Sunaga, D. Y., Chailangkarn, T., Nicol, X., Nunez, Y., Walker, M. F., Murdoch, J. D., Sanders, S. J., et al. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.141 · Cited by 236 · see citing works
Sodium Channel β Subunits: Emerging Targets in Channelopathies
O’Malley, H. A., & Isom, L. L. (2015) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021014-071846 · Cited by 236 · see citing works
Colasante, G., Lignani, G., Brusco, S., Berardino, C. D., Carpenter, J. C., Giannelli, S. G., Valassina, N., Bido, S., Ricci, R., Castoldi, V., et al. (2019) · Molecular Therapy · doi:10.1016/j.ymthe.2019.08.018 · Cited by 236 · see citing works
Han, S., Tai, C., Jones, C. J., Scheuer, T., & Catterall, W. A. (2014) · Neuron · doi:10.1016/j.neuron.2014.01.016 · Cited by 231 · see citing works
Self-citationClemizole and modulators of serotonin signalling suppress seizures in Dravet syndrome
Griffin, A., Hamling, K. R., Knupp, K. G., Hong, S., Lee, L. P., & Baraban, S. C. (2016) · Brain · doi:10.1093/brain/aww342 · Cited by 228 · see citing works
Dendritic Spine Plasticity: Function and Mechanisms
Runge, K., Cardoso, C., & de Chevigny, A. (2020) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2020.00036 · Cited by 224 · see citing works
Early hyperactivity and precocious maturation of corticostriatal circuits in Shank3B−/− mice
Peixoto, R. T., Wang, W., Croney, D. M., Kozorovitskiy, Y., & Sabatini, B. L. (2016) · Nature Neuroscience · doi:10.1038/nn.4260 · Cited by 219 · see citing works
Progress toward treatments for synaptic defects in autism
Delorme, R., Ey, E., Toro, R., Leboyer, M., Gillberg, C., & Bourgeron, T. (2013) · Nature Medicine · doi:10.1038/nm.3193 · Cited by 218 · see citing works
Silverman, J. L., Pride, M. C., Hayes, J. E., Puhger, K. R., Butler-Struben, H. M., Baker, S., & Crawley, J. N. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.66 · Cited by 215 · see citing works
Inhibitory control of the excitatory/inhibitory balance in psychiatric disorders
Selten, M. M., van Bokhoven, H., & Kasri, N. N. (2018) · F1000Research · doi:10.12688/f1000research.12155.1 · Cited by 208 · see citing works
The role of GABAergic signalling in neurodevelopmental disorders
Tang, X., Jaenisch, R., & Sur, M. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-021-00443-x · Cited by 206 · see citing works
Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses
Won, H., Mah, W., & Kim, E. (2013) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2013.00019 · Cited by 204 · see citing works
Lee, A. T., Vogt, D. L., Rubenstein, J. L. R., & Sohal, V. S. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1157-14.2014 · Cited by 202 · see citing works
Self-citationSodium channelopathies in neurodevelopmental disorders
Meisler, M. H., Hill, S. F., & Yu, W. (2021) · Nature reviews. Neuroscience · doi:10.1038/s41583-020-00418-4 · Cited by 202 · see citing works
Developmental and epileptic encephalopathies: from genetic heterogeneity to phenotypic continuum
Guerrini, R., Conti, V., Mantegazza, M., Balestrini, S., Galanopoulou, A. S., & Benfenati, F. (2023) · Physiological Reviews · doi:10.1152/physrev.00063.2021 · Cited by 196 · see citing works
Sodium Channels, Inherited Epilepsy, and Antiepileptic Drugs
Catterall, W. A. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140232 · Cited by 194 · see citing works
Self-citationDeidda, G., Bozarth, I. F., & Cancedda, L. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00119 · Cited by 192 · see citing works
Cortical interneuron development: a tale of time and space
Hu, J. S., Vogt, D., Sandberg, M., & Rubenstein, J. L. (2017) · Development · doi:10.1242/dev.132852 · Cited by 189 · see citing works
Self-citationMapping genetic modifiers of survival in a mouse model of Dravet syndrome
Miller, A. R., Hawkins, N. A., McCollom, C. E., & Kearney, J. A. (2013) · Genes Brain & Behavior · doi:10.1111/gbb.12099 · Cited by 185 · see citing works
Ogiwara, I., Iwasato, T., Miyamoto, H., Iwata, R., Yamagata, T., Mazaki, E., Yanagawa, Y., Tamamaki, N., Hensch, T. K., Itohara, S., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt331 · Cited by 183 · see citing works
Behavioral phenotypes of genetic mouse models of autism
Kazdoba, T. M., Leach, P. T., & Crawley, J. N. (2015) · Genes Brain & Behavior · doi:10.1111/gbb.12256 · Cited by 179 · see citing works
Yang, Y., Zhong, Z., Wang, B., Xia, X., Yao, W., Huang, L., Wang, Y., & Ding, W. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0437-1 · Cited by 179 · see citing works
Mistry, A. M., Thompson, C. H., Miller, A. R., Vanoye, C. G., George, A. L., & Kearney, J. A. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.01.006 · Cited by 177 · see citing works
Arid1b haploinsufficiency disrupts cortical interneuron development and mouse behavior
Jung, E., Moffat, J. J., Liu, J., Dravid, S. M., Gurumurthy, C. B., & Kim, W.-Y. (2017) · Nature Neuroscience · doi:10.1038/s41593-017-0013-0 · Cited by 177 · see citing works
GABAergic System Dysfunction in Autism Spectrum Disorders
Zhao, H., Mao, X., Zhu, C., Zou, X., Peng, F., Yang, W., Li, B., Li, G., Ge, T., & Cui, R. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.781327 · Cited by 172 · see citing works
Unifying Views of Autism Spectrum Disorders: A Consideration of Autoregulatory Feedback Loops
Mullins, C., Fishell, G., & Tsien, R. W. (2016) · Neuron · doi:10.1016/j.neuron.2016.02.017 · Cited by 167 · see citing works
Developmental and epileptic encephalopathies: what we do and do not know
Specchio, N., & Curatolo, P. (2020) · Brain · doi:10.1093/brain/awaa371 · Cited by 164 · see citing works
Favero, M., Sotuyo, N. P., Lopez, E., Kearney, J. A., & Goldberg, E. M. (2018) · The Journal of Neuroscience · doi:10.1523/jneurosci.0193-18.2018 · Cited by 163 · see citing works
Dravet syndrome—From epileptic encephalopathy to channelopathy
Brunklaus, A., & Zuberi, S. M. (2014) · Epilepsia · doi:10.1111/epi.12652 · Cited by 161 · see citing works
Forty Years of Sodium Channels: Structure, Function, Pharmacology, and Epilepsy
Catterall, W. A. (2017) · Neurochemical Research · doi:10.1007/s11064-017-2314-9 · Cited by 161 · see citing works
Self-citationPretzsch, C. M., Freyberg, J., Voinescu, B., Lythgoe, D. J., Horder, J., Méndez, M. A., Wichers, R., Ajram, L. A., Ivin, G., Heasman, M., et al. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-019-0333-8 · Cited by 156 · see citing works
Bhandari, R., Paliwal, J. K., & Kuhad, A. (2020) · Advances in neurobiology · doi:10.1007/978-3-030-30402-7_4 · Cited by 156 · see citing works
Convulsive seizures and SUDEP in a mouse model of SCN8A epileptic encephalopathy
Wagnon, J. L., Korn, M. J., Parent, R., Tarpey, T. A., Jones, J. M., Hammer, M. F., Murphy, G. G., Parent, J. M., & Meisler, M. H. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu470 · Cited by 154 · see citing works
Enhanced synapse remodelling as a common phenotype in mouse models of autism
Isshiki, M., Tanaka, S., Kuriu, T., Tabuchi, K., Takumi, T., & Okabe, S. (2014) · Nature Communications · doi:10.1038/ncomms5742 · Cited by 152 · see citing works
Major channels involved in neuropsychiatric disorders and therapeutic perspectives
Imbrici, P., Camerino, D. C., & Tricarico, D. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00076 · Cited by 148 · see citing works
Neuron-Glia Interactions in Neurodevelopmental Disorders
Kim, Y. S., Choi, J., & Yoon, B. (2020) · Cells · doi:10.3390/cells9102176 · Cited by 148 · see citing works
Dravet syndrome: a sodium channel interneuronopathy
Catterall, W. A. (2018) · Current Opinion in Physiology · doi:10.1016/j.cophys.2017.12.007 · Cited by 148 · see citing works
Self-citationKim, H., Lim, C., & Kaang, B. (2016) · Behavioral and Brain Functions · doi:10.1186/s12993-016-0087-y · Cited by 146 · see citing works
Krishnan, K., Wang, B.-S., Lu, J., Wang, L., Maffei, A., Cang, J., & Huang, Z. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1506499112 · Cited by 146 · see citing works
Sacai, H., Sakoori, K., Konno, K., Nagahama, K., Suzuki, H., Watanabe, T., Watanabe, M., Uesaka, N., & Kano, M. (2020) · Nature Communications · doi:10.1038/s41467-020-18861-3 · Cited by 145 · see citing works
Daily Oscillation of the Excitation-Inhibition Balance in Visual Cortical Circuits
Bridi, M., Zong, F., Min, X., Luo, N., Tran, T., Qiu, J., Severín, D., Zhang, X., Wang, G., Zhu, Z., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.11.011 · Cited by 139 · see citing works
Tau reduction prevents disease in a mouse model of <scp>D</scp> ravet syndrome
Gheyara, A. L., Ponnusamy, R., Djukic, B., Craft, R. J., Ho, K., Guo, W., Finucane, M. M., Sanchez, P. E., & Mucke, L. (2014) · Annals of Neurology · doi:10.1002/ana.24230 · Cited by 138 · see citing works
Genetic aspects of autism spectrum disorders: insights from animal models
Banerjee, S., Riordan, M., & Bhat, M. A. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00058 · Cited by 137 · see citing works
Yamagata, T., Raveau, M., Kobayashi, K., Miyamoto, H., Tatsukawa, T., Ogiwara, I., Itohara, S., Hensch, T. K., & Yamakawa, K. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104954 · Cited by 135 · see citing works
A human Dravet syndrome model from patient induced pluripotent stem cells
Higurashi, N., Uchida, T., Lossin, C., Misumi, Y., Okada, Y., Akamatsu, W., Imaizumi, Y., Zhang, B., Nabeshima, K., Mori, M. X., et al. (2013) · Molecular Brain · doi:10.1186/1756-6606-6-19 · Cited by 134 · see citing works
Dissecting the phenotypes of Dravet syndrome by gene deletion
Rubinstein, M., Han, S., Tai, C., Westenbroek, R. E., Hunker, A. C., Scheuer, T., & Catterall, W. A. (2015) · Brain · doi:10.1093/brain/awv142 · Cited by 133 · see citing works
Self-citationEffect of Seizures on the Developing Brain and Cognition
Holmes, G. L. (2016) · Seminars in Pediatric Neurology · doi:10.1016/j.spen.2016.05.001 · Cited by 133 · see citing works
Sodium channelopathies of skeletal muscle and brain
Mantegazza, M., Cestèle, S., & Catterall, W. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00025.2020 · Cited by 133 · see citing works
Self-citationSelective Na V 1.1 activation rescues Dravet syndrome mice from seizures and premature death
Richards, K., Milligan, C. J., Richardson, R. J., Jancovski, N., Grunnet, M., Jacobson, L. H., Undheim, E. A. B., Mobli, M., Chow, C. Y., Herzig, V., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1804764115 · Cited by 132 · see citing works
The Parvalbumin/Somatostatin Ratio Is Increased in Pten Mutant Mice and by Human PTEN ASD Alleles
Vogt, D. L., Cho, K. K. A., Lee, A. T., Sohal, V. S., & Rubenstein, J. L. R. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.019 · Cited by 130 · see citing works
Self-citationKovačević, J., Maroteaux, G., Schut, D., Loos, M., Dubey, M., Pitsch, J., Remmelink, E., Koopmans, B., Crowley, J. J., Cornelisse, L. N., et al. (2018) · Brain · doi:10.1093/brain/awy046 · Cited by 130 · see citing works
Lhx6 directly regulates Arx and CXCR7 to determine cortical interneuron fate and laminar position
Vogt, D., Hunt, R. F., Mandal, S., Sandberg, M., Silberberg, S. N., Nagasawa, T., Yang, Z., Baraban, S. C., & Rubenstein, J. L. R. (2014) · Neuron · doi:10.1016/j.neuron.2014.02.030 · Cited by 129 · see citing works
Self-citationDynamics of social representation in the mouse prefrontal cortex
Levy, D. R., Tamir, T., Kaufman, M., Parabucki, A., Weissbrod, A., Schneidman, E., & Yizhar, O. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0531-z · Cited by 127 · see citing works
Dravet Syndrome: Diagnosis and Long-Term Course
Connolly, M. B. (2016) · Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · doi:10.1017/cjn.2016.243 · Cited by 126 · see citing works
Cannabidiol: Recent advances and new insights for neuropsychiatric disorders treatment
Premoli, M., Aria, F., Bonini, S. A., Maccarinelli, G., Gianoncelli, A., Pina, S. D., Tambaro, S., Memo, M., & Mastinu, A. (2019) · Life Sciences · doi:10.1016/j.lfs.2019.03.053 · Cited by 125 · see citing works
Tanenhaus, A., Stowe, T., Young, A., McLaughlin, J., Aeran, R., Lin, I. W., Li, J., Hosur, R., Chen, M., Leedy, J., et al. (2022) · Human Gene Therapy · doi:10.1089/hum.2022.037 · Cited by 124 · see citing works
Yang, Y., Cheng, Z., Tang, H., Jiao, H., Sun, X., Cui, Q., Luo, F., Pan, H., Ma, C., & Li, B. (2016) · Cerebral Cortex · doi:10.1093/cercor/bhw121 · Cited by 124 · see citing works
Aberrant epilepsy-associated mutant Nav1.6 sodium channel activity can be targeted with cannabidiol
Patel, R. R., Barbosa, C., Brustovetsky, T., Brustovetsky, N., & Cummins, T. (2016) · Brain · doi:10.1093/brain/aww129 · Cited by 122 · see citing works
SCN1A Mutation—Beyond Dravet Syndrome: A Systematic Review and Narrative Synthesis
Ding, J., Li, X., Tian, H., Wang, L., Guo, B., Wang, Y., Li, W., Wang, F., & Sun, T. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.743726 · Cited by 121 · see citing works
Channelopathy pathogenesis in autism spectrum disorders
Schmunk, G., & Gargus, J. (2013) · Frontiers in Genetics · doi:10.3389/fgene.2013.00222 · Cited by 118 · see citing works
Drd3 Signaling in the Lateral Septum Mediates Early Life Stress-Induced Social Dysfunction
Shin, S., Pribiag, H., Lilascharoen, V., Knowland, D., Wang, X.-Y., & Lim, B. K. (2018) · Neuron · doi:10.1016/j.neuron.2017.11.040 · Cited by 120 · see citing works
Ward, J. (2018) · Cognitive Neuroscience · doi:10.1080/17588928.2018.1557131 · Cited by 120 · see citing works
Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits
Kanellopoulos, A. K., Mariano, V., Spinazzi, M., Woo, Y. J., Mclean, C., Pech, U., Li, K. W., Armstrong, J. D., Giangrande, A., Callaerts, P., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.044 · Cited by 114 · see citing works
Padilla, S. L., Perez, J. G., Ben-Hamo, M., Johnson, C. W., Sanchez, R. E. A., Bussi, I. L., Palmiter, R. D., & de la Iglesia, H. O. (2019) · Current Biology · doi:10.1016/j.cub.2019.01.022 · Cited by 113 · see citing works
Hou, Q.-L., Wang, Y., Li, Y., Chen, D., Yang, F., & Wang, S. (2018) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2018.00182 · Cited by 113 · see citing works
Functional significance of rare neuroligin 1 variants found in autism
Nakanishi, M., Nomura, J., Ji, X., Tamada, K., Arai, T., Takahashi, E., Bućan, M., & Takumi, T. (2017) · PLoS Genetics · doi:10.1371/journal.pgen.1006940 · Cited by 112 · see citing works
- Authors
- Han, S., Tai, C., Westenbroek, R. E., Yu, F. H., Cheah, C. S., Potter, G. B., Rubenstein, J. L., Scheuer, T., de la Iglesia, H. O., & Catterall, W. A.
- Affiliations
- University of Washington (US)
- University of California, San Francisco (US)
- Corresponding author
- Catterall, William A.
- ORCID
- Venue
- Nature
- Published
- 2012-08-22
- Volume
- 489
- Issue
- 7416
- Pages
- 385-390
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3448848
- OpenAlex
- W2050659319
- Cited by
- 643
- References
- 47
- Citations by year
- 2026: 23 · 2025: 35 · 2024: 43 · 2023: 57 · 2022: 39 · 2021: 62 · 2020: 54 · 2019: 48 · 2018: 37 · 2017: 55 · 2016: 49 · 2015: 47 · 2014: 44 · 2013: 48 · 2012: 2
- FWCI
- 31.70
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH075016, R37MH049428)
- National Institute of Neurological Disorders and Stroke (R01NS025704)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Keywords
- SCN1A, haploinsufficiency, GABAergic neurotransmission, GABAA receptor, clonazepam, social interaction deficits, hyperactivity, stereotypy, fear memory, spatial memory, interneurons, epilepsy, cognitive impairment
- MeSH terms
- Animals, Anxiety, Autistic Disorder, Clonazepam, Epilepsies, Myoclonic, gamma-Aminobutyric Acid, Heterozygote, Hippocampus, Hyperkinesis, Interneurons, Male, Memory, Nerve Tissue Proteins, Synaptic Transmission, Social Behavior, Space Perception, Syndrome, Transcription Factors, Sodium Channels, Homeodomain Proteins, GABA Modulators, Stereotypic Movement Disorder, Mice, Haploinsufficiency, GABAergic Neurons, NAV1.1 Voltage-Gated Sodium Channel
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
