Control of cortical GABA circuitry development by Nrg1 and ErbB4 signalling
Abstract
Schizophrenia is a complex disorder that interferes with the function of several brain systems required for cognition and normal social behaviour. Although the most notable clinical aspects of the disease only become apparent during late adolescence or early adulthood, many lines of evidence suggest that schizophrenia is a neurodevelopmental disorder with a strong genetic component. Several independent studies have identified neuregulin 1 (NRG1) and its receptor ERBB4 as important risk genes for schizophrenia, although their precise role in the disease process remains unknown. Here we show that Nrg1 and ErbB4 signalling controls the development of inhibitory circuitries in the mammalian cerebral cortex by cell-autonomously regulating the connectivity of specific GABA (gamma-aminobutyric acid)-containing interneurons. In contrast to the prevalent view, which supports a role for these genes in the formation and function of excitatory synapses between pyramidal cells, we found that ErbB4 expression in the mouse neocortex and hippocampus is largely confined to certain classes of interneurons. In particular, ErbB4 is expressed by many parvalbumin-expressing chandelier and basket cells, where it localizes to axon terminals and postsynaptic densities receiving glutamatergic input. Gain- and loss-of-function experiments, both in vitro and in vivo, demonstrate that ErbB4 cell-autonomously promotes the formation of axo-axonic inhibitory synapses over pyramidal cells, and that this function is probably mediated by Nrg1. In addition, ErbB4 expression in GABA-containing interneurons regulates the formation of excitatory synapses onto the dendrites of these cells. By contrast, ErbB4 is dispensable for excitatory transmission between pyramidal neurons. Altogether, our results indicate that Nrg1 and ErbB4 signalling is required for the wiring of GABA-mediated circuits in the postnatal cortex, providing a new perspective to the involvement of these genes in the aetiology of schizophrenia.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Preclinical animal models reproducing genetic vulnerabilities or environmental risk factors show anomalies in hippocampal and/or prefrontal parvalbumin interneurons.
“Recent studies have revealed anomalies in hippocampal and/or prefrontal PVI in many preclinical animal models aiming to reproduce genetic vulnerabilities (Carlson et al., 2011; Fazzari et al., 2010; Hikida et al., 2007; Wen et al., 2010) or environmental risk factors (Brown, 2011) such as prenatal maternal stress (Stevens et al., 2013), maternal and perinatal immune challenge (Jenkins et al., 2009”
From Redox dysregulation, neuroinflammation, and NMDA receptor hypofunction: A “central hub” in schizophrenia pathophysiology? (2016) · cites this paper as Fazzari et al., 2010
ErbB4 is restricted to specific interneuron types in the adult cortex but is present in most cortical interneurons around birth.
“Although the expression of ErbB4 is confined to specific types of interneuron in the adult cortex (Fazzari et al., 2010; Neddens and Buonanno, 2010; Vullhorst et al., 2009), ErbB4 is expressed in the majority of cortical interneurons at perinatal stages (Bean et al., 2014).”
From Development and Functional Diversification of Cortical Interneurons (2018) · cites this paper as Fazzari et al., 2010
Cites
Interneurons of the neocortical inhibitory system
Markram, H., Toledo-Rodriguez, M., Wang, Y., Gupta, A., Silberberg, G., & Wu, C. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1519 · Cited by 2,954 · see citing works
Parvalbumin neurons and gamma rhythms enhance cortical circuit performance
Sohal, V. S., Zhang, F., Yizhar, O., & Deisseroth, K. (2009) · Nature · doi:10.1038/nature07991 · Cited by 2,606 · see citing works
Driving fast-spiking cells induces gamma rhythm and controls sensory responses
Cardin, J. A., Carlén, M., Meletis, K., Knoblich, U., Zhang, F., Deisseroth, K., Tsai, L.-H., & Moore, C. I. (2009) · Nature · doi:10.1038/nature08002 · Cited by 2,603 · see citing works
Cortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297 · see citing works
Neuronal Diversity and Temporal Dynamics: The Unity of Hippocampal Circuit Operations
Klausberger, T., & Somogyi, P. (2008) · Science · doi:10.1126/science.1149381 · Cited by 2,050 · see citing works
Neuregulin 1 and Susceptibility to Schizophrenia
Stefánsson, H., Pétursson, H., Sigurðsson, E., Steinthórsdóttir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342734 · Cited by 1,671 · see citing works
Human gamma-frequency oscillations associated with attention and memory
Jensen, O. B., Kaiser, J., & Lachaux, J.-P. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.05.001 · Cited by 1,239 · see citing works
Schizophrenia as a Disorder of Neurodevelopment
Lewis, D. A., & Levitt, P. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142754 · Cited by 1,163 · see citing works
Aberrant neural and cardiac development in mice lacking the ErbB4 neuregulin receptor
Gassmann, M., Casagranda, F., Orioli, D., Simon, H. H., Lai, C., Klein, R., & Lemke, G. (1995) · Nature · doi:10.1038/378390a0 · Cited by 1,151 · see citing works
Rat hippocampal neurons in dispersed cell culture.
Banker, G. A., & Cowan, W. M. (1977) · Brain Research · doi:10.1016/0006-8993(77)90594-7 · Cited by 1,110 · see citing works
Neuregulin 1 in neural development, synaptic plasticity and schizophrenia
Mei, L., & Xiong, W.-C. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2392 · Cited by 1,030 · see citing works
The origin and specification of cortical interneurons
Wonders, C. P., & Anderson, S. A. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1954 · Cited by 980 · see citing works
Luján, R., Nusser, Z., Roberts, J. D. B., Shigemoto, R., & Somogyi, P. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01611.x · Cited by 863 · see citing works
Self-citationAbnormal neural synchrony in schizophrenia
Spencer, K. M., Nestor, P. G., Niznikiewicz, M. A., Salisbury, D. F., Shenton, M. E., & McCarley, R. W. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-19-07407.2003 · Cited by 624 · see citing works
NMDA-receptor-mediated, cell-specific integration of new neurons in adult dentate gyrus
Tashiro, A., Sandler, V. M., Toni, N., Zhao, C., & Gage, F. H. (2006) · Nature · doi:10.1038/nature05028 · Cited by 620 · see citing works
Genetic targeting of principal neurons in neocortex and hippocampus of NEX-Cre mice
Goebbels, S., Bormuth, I., Bode, U., Hermanson, O., Schwab, M. H., & Nave, K. (2006) · genesis · doi:10.1002/dvg.20256 · Cited by 579 · see citing works
Fuchs, E. C., Zivkovic, A. R., Cunningham, M. O., Middleton, S., LeBeau, F. E. N., Bannerman, D. M., Rozov, A., Whittington, M. A., Traub, R. D., Rawlins, J. N. P., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.031 · Cited by 532 · see citing works
Stenman, J. M., Toresson, H., & Campbell, K. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00167.2003 · Cited by 508 · see citing works
Gulyás, A. I., Megı́as, M., Emri, Z., & Freund, T. F. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-22-10082.1999 · Cited by 476 · see citing works
Short- and long-range attraction of cortical GABAergic interneurons by neuregulin-1
Flames, N., Long, J. E., Garratt, A. N., Fischer, T. M., Gassmann, M., Birchmeier, C., Lai, C., Rubenstein, J. L. R., & Marı́n, O. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.028 · Cited by 431 · see citing works
A subclass of prefrontal γ-aminobutyric acid axon terminals are selectively altered in schizophrenia
Woo, T.-U. W., Whitehead, R. E., Melchitzky, D. S., & Lewis, D. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.9.5341 · Cited by 410 · see citing works
The axo-axonic interneuron in the cerebral cortex of the rat, cat and monkey
Somogyi, P., Freund, T. F., & Cowey, A. (1982) · Neuroscience · doi:10.1016/0306-4522(82)90086-0 · Cited by 392 · see citing works
Regulation of Neuregulin Signaling by PSD-95 Interacting with ErbB4 at CNS Synapses
Huang, Y. Z., Won, S., Ali, D. W., Wang, Q., Tanowitz, M., Du, Q., Pelkey, K. A., Yang, D. J., Xiong, W., Salter, M. W., et al. (2000) · Neuron · doi:10.1016/s0896-6273(00)81176-9 · Cited by 381 · see citing works
The Neuregulin-1 Receptor ErbB4 Controls Glutamatergic Synapse Maturation and Plasticity
Li, B., Woo, R.-S., Mei, L., & Malinow, R. (2007) · Neuron · doi:10.1016/j.neuron.2007.03.028 · Cited by 354 · see citing works
The molecular genetics of schizophrenia: new findings promise new insights
Owen, M. J., Williams, N. M., & O’Donovan, M. C. (2003) · Molecular Psychiatry · doi:10.1038/sj.mp.4001444 · Cited by 322 · see citing works
Neuregulin-1 Enhances Depolarization-Induced GABA Release
Woo, R., Li, X.-M., Tao, Y., Carpenter‐Hyland, E. P., Huang, Y. Z., Weber, J., Neiswender, H., Dong, X., Wu, J., Gassmann, M., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.04.009 · Cited by 297 · see citing works
Preferential Origin and Layer Destination of GAD65-GFP Cortical Interneurons
López‐Bendito, G. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhh072 · Cited by 288 · see citing works
Tamás, G., Buhl, E. H., & Somogyi, P. (1997) · The Journal of Physiology · doi:10.1113/jphysiol.1997.sp022054 · Cited by 278 · see citing works
The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses
Garcia, R. A. G., Vasudevan, K., & Buonanno, A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.7.3596 · Cited by 278 · see citing works
Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality
Tidcombe, H., Jackson-Fisher, A. J., Mathers, K., Stern, D. F., Gassmann, M., & Golding, J. P. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1436402100 · Cited by 255 · see citing works
A neuregulin 1 variant associated with abnormal cortical function and psychotic symptoms
Hall, J., Whalley, H. C., Job, D. E., Baig, B. J., McIntosh, A. M., Evans, K. L., Thomson, P. A., Porteous, D. J., Owens, D. G. C., Johnstone, E. C., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1795 · Cited by 241 · see citing works
Selective Expression of ErbB4 in Interneurons, But Not Pyramidal Cells, of the Rodent Hippocampus
Vullhorst, D., Neddens, J., Karavanova, I. D., Tricoire, L., Petralia, R. S., McBain, C. J., & Buonanno, A. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.2454-09.2009 · Cited by 221 · see citing works
Barros, C. S., Calabrese, B., Chamero, P., Roberts, A. J., Korzus, E., Lloyd, K., Stowers, L., Mayford, M., Halpain, S., & Müller, U. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900355106 · Cited by 197 · see citing works
Self-citationNeuregulin receptors, erbB3 and erbB4, are localized at neuromuscular synapses.
Zhu, X., Lai, C., Thomas, S. Μ., & Burden, S. J. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb00272.x · Cited by 178 · see citing works
Bjarnadóttir, M., Misner, D., Haverfield-Gross, S., Bruun, S., Helgason, V. G., Stefánsson, H., Sigmundsson, A., Firth, D. R., Nielsen, B., Stefansdottir, R., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.4314-06.2007 · Cited by 176 · see citing works
Neuregulin-1 Reverses Long-Term Potentiation at CA1 Hippocampal Synapses
Kwon, O., Longart, M., Vullhorst, D., Hoffman, D. A., & Buonanno, A. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2100-05.2005 · Cited by 171 · see citing works
Behavioral characteristics of a nervous system-specific erbB4 knock-out mouse
Golub, M. S., Germann, S. L., & Lloyd, K. C. K. (2004) · Behavioural Brain Research · doi:10.1016/j.bbr.2003.11.010 · Cited by 155 · see citing works
Self-citationLayer acquisition by cortical GABAergic interneurons is independent of Reelin signaling
Pla, R., Borrell, V., Flames, N., & Marín, O. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0245-06.2006 · Cited by 151 · see citing works
Self-citationKrivosheya, D., Tapia, L., Levinson, J. N., Huang, K., Kang, Y., Hines, R. M., Ting, A. K. L., Craig, A. M., Mei, L., Bamji, S. X., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800073200 · Cited by 128 · see citing works
A Mosaic of Functional Kainate Receptors in Hippocampal Interneurons
Christensen, J. K., Paternain, A. V., Selak, S., Ahring, P. K., & Lerma, J. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2156-04.2004 · Cited by 127 · see citing works
Self-citationAddington, A. M., Gornick, M. C., Shaw, P., Seal, J., Gogtay, N., GREENSTEIN, D. K., CLASEN, L. S., Coffey, M., Gochman, P., Long, R. T. L., et al. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001906 · Cited by 109 · see citing works
Regulation of ErbB-4 endocytosis by neuregulin in GABAergic hippocampal interneurons
Longart, M., Chatani-Hinze, M., González, C. M., Vullhorst, D., & Buonanno, A. (2007) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2007.02.014 · Cited by 29 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Verret, L., Mann, E. O., Hang, G. B., Barth, A. M. I., Cobos, I., Ho, K., Devidze, N., Masliah, E., Kreitzer, A. C., Mody, I., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.046 · Cited by 1,216 · see citing works
Hu, H., Gan, J., & Jonas, P. (2014) · Science · doi:10.1126/science.1255263 · Cited by 1,197 · see citing works
Interneuron dysfunction in psychiatric disorders
Marín, O. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3155 · Cited by 1,190 · 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
Hippocampal GABAergic Inhibitory Interneurons
Pelkey, K. A., Chittajallu, R., Craig, M. T., Tricoire, L., Wester, J. C., & McBain, C. J. (2017) · Physiological Reviews · doi:10.1152/physrev.00007.2017 · Cited by 889 · see citing works
Development and Functional Diversification of Cortical Interneurons
Lim, L., Mi, D., Llorca, A., & Marín, O. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.009 · Cited by 714 · see citing works
Neuregulin-ERBB Signaling in the Nervous System and Neuropsychiatric Diseases
Mei, L., & Nave, K. (2014) · Neuron · doi:10.1016/j.neuron.2014.06.007 · Cited by 590 · see citing works
Maroof, A. M., Keros, S., Tyson, J. A., Ying, S.-W., Ganat, Y. M., Merkle, F. T., Liu, B., Goulburn, A., Stanley, E. G., Elefanty, A. G., et al. (2013) · Cell Stem Cell · doi:10.1016/j.stem.2013.04.008 · Cited by 596 · see citing works
Nicholas, C. R., Chen, J., Tang, Y., Southwell, D. G., Chalmers, N., Vogt, D. L., Arnold, C. M., Chen, Y.-J. J., Stanley, E. G., Elefanty, A. G., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2013.04.005 · Cited by 513 · see citing works
Gao, R., & Penzes, P. (2015) · Current Molecular Medicine · doi:10.2174/1566524015666150303003028 · Cited by 516 · see citing works
“3) ErbB4 is not necessary for excitatory transmission between pyramidal neurons [87].”
BackgroundResultGABAergic Interneurons Shape the Functional Maturation of the Cortex
Le Magueresse, C., & Monyer, H. (2013) · Neuron · doi:10.1016/j.neuron.2013.01.011 · Cited by 425 · see citing works
Spiegel, I., Mardinly, A. R., Gabel, H. W., Bazinet, J. E., Couch, C. H., Tzeng, C. P., Harmin, D. A., & Greenberg, M. E. (2014) · Cell · doi:10.1016/j.cell.2014.03.058 · Cited by 416 · see citing works
“Npas4-Regulated Genes Induced by Sensory Experience in SST Neurons Can Modify Excitatory Synapses Despite the recent identification of molecules that shape the synaptic connectivity of inhibitory neurons (Fazzari et al., 2010; Sylwestrak andGhosh, 2012), themolecular mechanisms underlying the plasticity of synaptic in…”
Steullet, P., Cabungcal, J.-H., Coyle, J., Didriksen, M., Gill, K., Grace, A. A., Hensch, T. K., LaMantia, A.-S., Lindemann, L., Maynard, T. M., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.47 · Cited by 360 · see citing works
Erbb4 Deletion from Fast-Spiking Interneurons Causes Schizophrenia-like Phenotypes
del Pino, I., García-Frigola, C., Dehorter, N., Brotons-Mas, J. R., Alvarez-Salvado, E., Martínez de Lagrán, M., Ciceri, G., Gabaldón, M. V., Moratal, D., Dierssen, M., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.07.010 · Cited by 314 · see citing works
Self-citationHippocampal-Prefrontal Interactions in Cognition, Behavior and Psychiatric Disease
Sigurdsson, T., & Duvarci, S. (2016) · Frontiers in Systems Neuroscience · doi:10.3389/fnsys.2015.00190 · Cited by 309 · see citing works
Pyramidal cell regulation of interneuron survival sculpts cortical networks
Wong, F. K., Bercsenyi, K., Sreenivasan, V., Portalés, A., Fernández-Otero, M., & Marín, O. (2018) · Nature · doi:10.1038/s41586-018-0139-6 · Cited by 286 · see citing works
The origin of NMDA receptor hypofunction in schizophrenia
Nakazawa, K., & Sapkota, K. (2019) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2019.107426 · Cited by 277 · see citing works
Behavior-dependent specialization of identified hippocampal interneurons
Lapray, D., Lasztóczi, B., Lagler, M., Viney, T. J., Katona, L., Valenti, O., Hartwich, K., Borhegyi, Z., Somogyi, P., & Klausberger, T. (2012) · Nature Neuroscience · doi:10.1038/nn.3176 · Cited by 262 · see citing works
Steullet, P., Cabungcal, J. H., Monin, A., Dwir, D., O'Donnell, P., Cuenod, M., & Do, K. Q. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2014.06.021 · Cited by 262 · see citing works
GABA Neuron Alterations, Cortical Circuit Dysfunction and Cognitive Deficits in Schizophrenia
González‐Burgos, G., Fish, K. N., & Lewis, D. A. (2011) · Neural Plasticity · doi:10.1155/2011/723184 · Cited by 244 · see citing works
Pelkey, K. A., Barksdale, E., Craig, M. T., Yuan, X., Sukumaran, M., Vargish, G. A., Mitchell, R. M., Wyeth, M. S., Petralia, R. S., Chittajallu, R., et al. (2015) · Neuron · doi:10.1016/j.neuron.2015.02.020 · Cited by 245 · see citing works
Neurodevelopment, GABA System Dysfunction, and Schizophrenia
Schmidt, M. J., & Mirnics, K. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.95 · Cited by 239 · see citing works
Chen, Y., Zhang, M., Yin, D., Wen, L., Ting, A. K. L., Wang, P., Lu, Y.-S., Zhu, X.-H., Li, S.-J., Wu, C.-Y., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010669107 · Cited by 237 · see citing works
Martínez‐Losa, M., Tracy, T. E., Ma, K., Verret, L., Clemente-Perez, A., Khan, A. S., Cobos, I., Ho, K., Gan, L., Mucke, L., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.02.029 · Cited by 233 · see citing works
Oxidative Stress‐Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives
Ermakov, E. A., Dmitrieva, E. M., Parshukova, D. A., Kazantseva, D. V., Vasilieva, A. R., & Smirnova, L. P. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/8881770 · Cited by 252 · see citing works
Distinct molecular programs regulate synapse specificity in cortical inhibitory circuits
Favuzzi, E., Deogracias, R., Marques–Smith, A., Maeso, P. A., Jézéquel, J., Exposito-Alonso, D., Balia, M., Kroon, T., Hinojosa, A. J., Maraver, E. F., et al. (2019) · Science · doi:10.1126/science.aau8977 · Cited by 217 · see citing works
Self-citationMcKlveen, J. M., Morano, R. L., Fitzgerald, M., Zoubovsky, S., Cassella, S. N., Scheimann, J. R., Ghosal, S., Mahbod, P., Packard, B. A., Myers, B., et al. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.03.2101 · Cited by 224 · 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
Neuregulin 1 Promotes Excitatory Synapse Development and Function in GABAergic Interneurons
Ting, A. K. L., Chen, Y., Wen, L., Yin, D., Shen, C., Tao, Y., Liu, X., Xiong, W., & Mei, L. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.2538-10.2011 · Cited by 216 · see citing works
Generation of interneuron diversity in the mouse cerebral cortex
Gelman, D. M., & Marín, O. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07267.x · Cited by 188 · see citing works
Cortical interneurons in autism
Contractor, A., Ethell, I. M., & Portera‐Cailliau, C. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00967-6 · Cited by 180 · see citing works
Cntnap4 differentially contributes to GABAergic and dopaminergic synaptic transmission
Karayannis, T., Au, E., Patel, J. C., Kruglikov, I., Markx, S., Delorme, R., Héron, D., Salomon, D., Glessner, J., Restituito, S., et al. (2014) · Nature · doi:10.1038/nature13248 · Cited by 183 · see citing works
Neuroplasticity signaling pathways linked to the pathophysiology of schizophrenia
Balu, D. T., & Coyle, J. T. (2010) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.10.005 · Cited by 182 · see citing works
Shamir, A., Kwon, O., Karavanova, I. D., Vullhorst, D., Leiva‐Salcedo, E., Janssen, M. J., & Buonanno, A. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.1899-11.2012 · Cited by 174 · see citing works
Specific Regulation of NRG1 Isoform Expression by Neuronal Activity
Liu, X., Bates, R. C., Yin, D., Shen, C., Wang, F., Su, N. Y., Kirov, S. A., Luo, Y., Wang, J.-Z., Xiong, W., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5317-10.2011 · Cited by 174 · see citing works
Marques-Smith, A., Lyngholm, D., Kaufmann, A.-K., Stacey, J. A., Hoerder-Suabedissen, A., Becker, E. B. E., Wilson, M. C., Molnár, Z., & Butt, S. J. B. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.015 · Cited by 173 · see citing works
Neuregulin 1 regulates excitability of fast-spiking neurons through Kv1.1 and acts in epilepsy
Li, K.-X., Lu, Y.-M., Xu, Z.-H., Zhang, J., Zhu, J.-M., Zhang, J.-M., Cao, S.-X., Chen, X.-J., Chen, Z., Luo, J.-H., et al. (2012) · Nature Neuroscience · doi:10.1038/nn.3006 · Cited by 173 · see citing works
The neuregulin signaling pathway and schizophrenia: From genes to synapses and neural circuits
Buonanno, A. (2010) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2010.07.012 · Cited by 172 · see citing works
Development and specification of GABAergic cortical interneurons
Kelsom, C., & Lu, W. (2013) · Cell & Bioscience · doi:10.1186/2045-3701-3-19 · Cited by 171 · see citing works
Tuning of fast-spiking interneuron properties by an activity-dependent transcriptional switch
Dehorter, N., Ciceri, G., Bartolini, G., Lim, L., del Pino, I., & Marín, O. (2015) · Science · doi:10.1126/science.aab3415 · Cited by 169 · see citing works
Murray, A., Wołoszynowska-Fraser, M. U., Ansel-Bollepalli, L., Marshall-Phelps, K. L., Foggetti, A., Crouch, B., Riedel, G., & Wulff, P. (2015) · Scientific Reports · doi:10.1038/srep16778 · Cited by 165 · see citing works
The contribution of GABAergic dysfunction to neurodevelopmental disorders
Ramamoorthi, K., & Lin, Y. (2011) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2011.03.003 · Cited by 169 · see citing works
Powell, S. B., Sejnowski, T. J., & Behrens, M. M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.01.049 · Cited by 164 · see citing works
Inan, M., Welagen, J., & Anderson, S. A. (2012) · Cerebral Cortex · doi:10.1093/cercor/bhr148 · Cited by 161 · see citing works
GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia
Xu, M., & Wong, A. H. C. (2018) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.172 · Cited by 159 · see citing works
Do, K. Q., Cuenod, M., & Hensch, T. K. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv065 · Cited by 158 · see citing works
A Central Extended Amygdala Circuit That Modulates Anxiety
Ahrens, S., Wu, M. V., Furlan, A., Hwang, G., Paik, R., Li, H., Penzo, M. A., Tollkühn, J., & Li, B. (2018) · Journal of Neuroscience · doi:10.1523/jneurosci.0705-18.2018 · Cited by 151 · see citing works
Law, A. J., Wang, Y., Sei, Y., O’Donnell, P., Piantadosi, P., Papaleo, F., Straub, R. E., Huang, W., Thomas, C. J., Vakkalanka, R., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1206118109 · Cited by 147 · see citing works
Adolescent Onset of Cortical Disinhibition in Schizophrenia: Insights From Animal Models
O'Donnell, P. (2011) · Schizophrenia Bulletin · doi:10.1093/schbul/sbr028 · Cited by 145 · see citing works
Iwakura, Y., & Nawa, H. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00004 · Cited by 145 · see citing works
Neuregulin-1/ErbB network: An emerging modulator of nervous system injury and repair
Kataria, H., Alizadeh, A., & Karimi‐Abdolrezaee, S. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101643 · Cited by 138 · see citing works
Reversal of Behavioral Deficits and Synaptic Dysfunction in Mice Overexpressing Neuregulin 1
Yin, D., Chen, Y., Lu, Y.-S., Bean, J. C., Sathyamurthy, A., Shen, C., Liu, X., Lin, T. W., Smith, C. A., Xiong, W., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.03.028 · Cited by 139 · see citing works
Primary Cilia Signaling Shapes the Development of Interneuronal Connectivity
Guo, J., Otis, J. M., Higginbotham, H., Monckton, C., Cheng, J., Asokan, A., Mykytyn, K., Caspary, T., Stuber, G. D., & Anton, E. S. (2017) · Developmental Cell · doi:10.1016/j.devcel.2017.07.010 · Cited by 136 · see citing works
Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits
Batista-Brito, R., Vinck, M., Ferguson, K. A., Chang, J. T., Laubender, D., Lur, G., Mossner, J. M., Hernandez, V. G., Ramakrishnan, C., Deisseroth, K., et al. (2017) · Neuron · doi:10.1016/j.neuron.2017.07.034 · Cited by 135 · see citing works
Rivero, O., Selten, M. M., Sich, S., Popp, S., Bacmeister, L., Amendola, E., Negwer, M., Schubert, D., Proft, F., Kiser, D. P., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.152 · Cited by 127 · see citing works
ErbB4 regulation of a thalamic reticular nucleus circuit for sensory selection
Ahrens, S., Jaramillo, S., Yu, K., Ghosh, S., Hwang, G., Paik, R., Lai, C., He, M., Huang, Z. J., & Li, B. (2014) · Nature Neuroscience · doi:10.1038/nn.3897 · Cited by 127 · see citing works
Neuregulin 1 represses limbic epileptogenesis through ErbB4 in parvalbumin-expressing interneurons
Tan, G., Liu, Y.-Y., Hu, X.-L., Yin, D., Mei, L., & Xiong, Z. (2011) · Nature Neuroscience · doi:10.1038/nn.3005 · Cited by 124 · see citing works
Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders
Penzes, P., Buonanno, A., Passafaro, M., Sala, C., & Sweet, R. A. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12261 · Cited by 125 · see citing works
Role of BACE1 in Alzheimer’s synaptic function
Das, B., & Yan, R. (2017) · Translational Neurodegeneration · doi:10.1186/s40035-017-0093-5 · Cited by 122 · see citing works
The Role of Parvalbumin Interneurons in Neurotransmitter Balance and Neurological Disease
Nahar, L., Delacroix, B. M., & Nam, H. W. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.679960 · Cited by 118 · see citing works
Neuregulin-1/ErbB4 Signaling Regulates Visual Cortical Plasticity
Sun, Y., Ikrar, T., Davis, M. F., Gong, N., Zheng, X., Luo, Z. D., Lai, C., Mei, L., Holmes, T. C., Gandhi, S. P., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.08.033 · Cited by 117 · see citing works
The rise of a new GABA pharmacology
Möhler, H. (2010) · Neuropharmacology · doi:10.1016/j.neuropharm.2010.10.020 · Cited by 111 · see citing works
Glutamate in schizophrenia: Neurodevelopmental perspectives and drug development
Egerton, A., Grace, A. A., Stone, J. M., Bossong, M. G., Sand, M. S., & McGuire, P. K. (2020) · Schizophrenia Research · doi:10.1016/j.schres.2020.09.013 · Cited by 113 · see citing works
Hoftman, G. D., Datta, D., & Lewis, D. A. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.05.022 · Cited by 109 · see citing works
Developmental pathology, dopamine, stress and schizophrenia
Lodge, D. J., & Grace, A. A. (2011) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2010.08.002 · Cited by 109 · see citing works
Dysregulated Expression of Neuregulin-1 by Cortical Pyramidal Neurons Disrupts Synaptic Plasticity
Agarwal, A., Zhang, M., Trembak-Duff, I., Unterbarnscheidt, T., Radyushkin, K., Dibaj, P., Martins‐de‐Souza, D., Boretius, S., Brzózka, M. M., Steffens, H., et al. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.07.026 · Cited by 105 · see citing works
Maturation-Promoting Activity of SATB1 in MGE-Derived Cortical Interneurons
Denaxa, M., Kalaitzidou, M., Garefalaki, A., Achimastou, A., Lasrado, R., Maes, T., & Pachnis, V. (2012) · Cell Reports · doi:10.1016/j.celrep.2012.10.003 · Cited by 105 · see citing works
Bean, J. C., Lin, T. W., Sathyamurthy, A., Liu, F., Yin, D.-M., Xiong, W.-C., & Mei, L. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.2021-14.2014 · Cited by 105 · see citing works
GABAergic Circuit Dysfunctions in Neurodevelopmental Disorders
Chattopadhyaya, B., & Cristo, G. D. (2012) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2012.00051 · Cited by 105 · see citing works
Crabtree, G. W., & Gogos, J. A. (2014) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2014.00028 · Cited by 102 · see citing works
Involvement of cortical fast-spiking parvalbumin-positive basket cells in epilepsy
Jiang, X., Lachance, M., & Rossignol, E. (2016) · Progress in brain research · doi:10.1016/bs.pbr.2016.04.012 · Cited by 98 · see citing works
Teixeira, C. M., Martín, E. D., Sahún, I., Masachs, N., Pujadas, L., Corvelo, A., Bosch, C., Rossi, D. P., Martı́nez, A., Maldonado, R. J., et al. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2011.153 · Cited by 102 · see citing works
The Enigmatic Function of Chandelier Cells
Woodruff, A. R., Anderson, S. A., & Yuste, R. (2010) · Frontiers in Neuroscience · doi:10.3389/fnins.2010.00201 · Cited by 97 · see citing works
Activity-Dependent Plasticity of Axo-axonic Synapses at the Axon Initial Segment
Pan-Vazquez, A., Wefelmeyer, W., Sabater, V. G., Neves, G., & Burrone, J. (2020) · Neuron · doi:10.1016/j.neuron.2020.01.037 · Cited by 99 · see citing works
Losing your inhibition: Linking cortical GABAergic interneurons to schizophrenia
Inan, M., Petros, T. J., & Anderson, S. A. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.11.013 · Cited by 100 · see citing works
Abnormal wiring of CCK+ basket cells disrupts spatial information coding
del Pino, I., Brotons‐Mas, J. R., Marques–Smith, A., Marighetto, A., Frick, A., Marín, Ó., & Rico, B. (2017) · Nature Neuroscience · doi:10.1038/nn.4544 · Cited by 96 · see citing works
Self-citationPrenatal stress and inhibitory neuron systems: implications for neuropsychiatric disorders
Fine, R., Zhang, J., & Stevens, H. E. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.35 · Cited by 96 · see citing works
Neurosteroid Actions in Memory and Neurologic/Neuropsychiatric Disorders
Ratner, M. H., Kumaresan, V., & Farb, D. H. (2019) · Frontiers in Endocrinology · doi:10.3389/fendo.2019.00169 · Cited by 96 · see citing works
Maintenance of GABAergic Activity by Neuregulin 1-ErbB4 in Amygdala for Fear Memory
Lu, Y., Sun, X.-D., Hou, F., Bi, L., Yin, D., Liu, F., Chen, Y., Bean, J. C., Jiao, H.-F., Liu, X., et al. (2014) · Neuron · doi:10.1016/j.neuron.2014.09.029 · Cited by 95 · see citing works
Neddens, J., Fish, K. N., Tricoire, L., Vullhorst, D., Shamir, A., Chung, W., Lewis, D. A., McBain, C. J., & Buonanno, A. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.04.016 · Cited by 95 · see citing works
Neural circuit dysfunction in mouse models of neurodevelopmental disorders
del Pino, I., Rico, B., & Marín, Ó. (2018) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.12.013 · Cited by 94 · see citing works
Self-citationDense and Overlapping Innervation of Pyramidal Neurons by Chandelier Cells
Inan, M., Blázquez‐Llorca, L., Merchán-Pérez, Á., Anderson, S. A., DeFelipe, J., & Yuste, R. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4049-12.2013 · Cited by 91 · see citing works
Cognition in transmembrane domain neuregulin 1 mutant mice
Duffy, L., Cappas, E., Lai, D., Boucher, A. A., & Karl, T. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.07.042 · Cited by 92 · see citing works
Dlx1andDlx2Promote Interneuron GABA Synthesis, Synaptogenesis, and Dendritogenesis
Pla, R., Stanco, A., Howard, M. A., Rubin, A. N., Vogt, D. L., Mortimer, N., Cobos, I., Potter, G. B., Lindtner, S., Price, J. D., et al. (2017) · Cerebral Cortex · doi:10.1093/cercor/bhx241 · Cited by 93 · see citing works
Self-citationRass, O., Forsyth, J. K., Krishnan, G. P., Hetrick, W. P., Klaunig, M. J., Breier, A. F., O’Donnell, B. F., & Brenner, C. A. (2012) · Schizophrenia Research · doi:10.1016/j.schres.2012.01.003 · Cited by 92 · see citing works
Neuregulin signaling, cortical circuitry development and schizophrenia
Rico, B., & Marín, Ó. (2011) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2010.12.010 · Cited by 90 · see citing works
Self-citationMassi, L., Lagler, M., Hartwich, K., Borhegyi, Z., Somogyi, P., & Klausberger, T. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.3475-12.2012 · Cited by 88 · see citing works
Dysregulated ErbB4 Splicing in Schizophrenia: Selective Effects on Parvalbumin Expression
Chung, D. W., Volk, D. W., Arion, D., Zhang, Y., Sampson, A. R., & Lewis, D. A. (2016) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2015.15020150 · Cited by 86 · see citing works
Volk, D. W., & Lewis, D. A. (2014) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu111 · Cited by 86 · see citing works
Tai, Y., Gallo, N. B., Wang, M., Yu, J.-R., & Aelst, L. V. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.009 · Cited by 85 · see citing works
Neuronal migration abnormalities and its possible implications for schizophrenia
Muraki, K., & Tanigaki, K. (2015) · Frontiers in Neuroscience · doi:10.3389/fnins.2015.00074 · Cited by 83 · see citing works
Synaptic Dysfunction in Schizophrenia
Yin, D., Chen, Y., Sathyamurthy, A., Xiong, W., & Mei, L. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-3-7091-0932-8_22 · Cited by 81 · see citing works
Dynamic ErbB4 Activity in Hippocampal-Prefrontal Synchrony and Top-Down Attention in Rodents
Tan, Z., Robinson, H. L., Yin, D., Liu, Y., Liu, F., Wang, H., Lin, T. W., Xing, G., Gan, L., Xiong, W., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.03.018 · Cited by 80 · see citing works
Neuregulin-1 and schizophrenia in the genome-wide association study era
Mostaid, M. S., Lloyd, D., Liberg, B., Sundram, S., Pereira, A. M., Pantelis, C., Karl, T., Weickert, C. S., Everall, I., & Bousman, C. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.06.001 · Cited by 78 · see citing works
Deakin, I. H., Nissen, W., Law, A. J., Lane, T. A., Kanso, R., Schwab, M. H., Nave, K., Lamsa, K. P., Paulsen, O., Bannerman, D. M., et al. (2011) · Cerebral Cortex · doi:10.1093/cercor/bhr223 · Cited by 78 · see citing works
Neuregulin 3 promotes excitatory synapse formation on hippocampal interneurons
Müller, T. H., Braud, S., Jüttner, R., Voigt, B. C., Paulick, K., Sheean, M. E., Klisch, C., Güneykaya, D., Rathjen, F. G., Geiger, J. R., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201798858 · Cited by 77 · see citing works
Development of Cortical Interneurons
Chu, J., & Anderson, S. A. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.171 · Cited by 76 · see citing works
Increased cortical reactivity to repeated tones at 8 months in infants with later ASD
Kolesnik, A., Begum Ali, J., Gliga, T., Guiraud, J., Charman, T., Johnson, M. H., Jones, E. J. H., & The BASIS Team (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0393-x · Cited by 75 · see citing works
Hagenauer, M. H., Schulmann, A., Li, J. Z., Vawter, M. P., Walsh, D. M. A., Thompson, R. C., Turner, C. A., Bunney, W. E., Myers, R., Barchas, J. D., et al. (2018) · PLoS ONE · doi:10.1371/journal.pone.0200003 · Cited by 76 · see citing works
Gu, Y., Tran, T., Murase, S., Borrell, A., Kirkwood, A., & Quinlan, E. M. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.4242-15.2016 · Cited by 74 · see citing works
- Authors
- Fazzari, P., Paternain, A. V., Valiente, M., Pla, R., Luján, R., Lloyd, K., Lerma, J., Marín, O., & Rico, B.
- Affiliations
- Consejo Superior de Investigaciones Científicas (ES)
- University of Castilla-La Mancha (ES)
- University of California, Davis (US)
- Corresponding author
- Rico, Beatriz
- ORCID
- Venue
- Nature
- Published
- 2010-04
- Volume
- 464
- Issue
- 7293
- Pages
- 1376-1380
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2031755128
- Cited by
- 501
- References
- 42
- Citations by year
- 2026: 18 · 2025: 19 · 2024: 24 · 2023: 28 · 2022: 28 · 2021: 48 · 2020: 23 · 2019: 26 · 2018: 34 · 2017: 29 · 2016: 35 · 2015: 29 · 2014: 39 · 2013: 30 · 2012: 28
- FWCI
- 15.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- neuregulin-1, ErbB4, schizophrenia, GABAergic interneurons, cortical circuit development, axo-axonic synapses, parvalbumin interneurons, chandelier cells, basket cells, synaptic adhesion proteins, neurodevelopmental disorders, neocortex, hippocampus, inhibitory synapse formation, genetic risk factors
- MeSH terms
- Animals, Cell Differentiation, Cerebral Cortex, Dendrites, Embryo, Mammalian, Female, gamma-Aminobutyric Acid, Interneurons, Neural Inhibition, Neural Pathways, Schizophrenia, Synapses, Signal Transduction, Pyramidal Cells, Excitatory Postsynaptic Potentials, Neuregulin-1, Mice, ErbB Receptors, Receptor, ErbB-4, In Vitro Techniques
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