Home LiteratureArticle Details
PMID: 18185097 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

ErbB4 is a suppressor of long-term potentiation in the adult hippocampus.

Neuroreport ·Vol. 19 ·No. 2 ·2008-01-22 ·Pages 139-43

Pitcher GM, Beggs S, Woo RS, Mei L, Salter MW

Abstract

ErbB4 has emerged as a leading susceptibility gene for schizophrenia but the function of the ErbB4 receptor in the adult brain is unknown. Here, we show in the adult hippocampus that long-term potentiation (LTP) of transmission at Schaffer collateral CA1 synapses was markedly enhanced in mutant mice lacking ErbB4. Concordantly, LTP was enhanced by acutely blocking ErbB4 in wild-type animals, indicating that ErbB4 activity constitutively suppresses LTP. Moreover, increasing ErbB4 signaling further suppressed LTP. By contrast, altering ErbB4 activity did not affect basal synaptic transmission or short-term facilitation. Our findings suggest that cognitive deficits in schizophrenia may be a consequence of hyperfunction of ErbB4 signaling leading to suppressed glutamatergic synaptic plasticity, thus opening new approaches for the treatment of this disorder.

MeSH Terms
Animals Cognition Disorders/genetics,metabolism,physiopathology Down-Regulation/genetics ErbB Receptors/genetics Hippocampus/cytology,metabolism Long-Term Potentiation/genetics Male Mice Mice, Knockout Neural Pathways/cytology,metabolism Organ Culture Techniques Rats Rats, Sprague-Dawley Receptor, ErbB-4 Schizophrenia/genetics,metabolism,physiopathology Synaptic Transmission/genetics Theta Rhythm
Chemicals
ErbB Receptors Erbb4 protein, mouse Erbb4 protein, rat Receptor, ErbB-4
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Pitcher Graham M
Program in Neurosciences & Mental Health, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. [email protected]
Beggs Simon
Woo Ran-Sook
Mei Lin
Salter Michael W
References (25)
25 references, click to expand
  1. Evidence that interaction between neuregulin 1 and its receptor erbB4 increases susceptibility to schizophrenia.
    Am J Med Genet B Neuropsychiatr Genet. 2006 Jan 5;141B(1):96-101 PMID: 16249994
  2. Neuregulin-1 reverses long-term potentiation at CA1 hippocampal synapses.
    J Neurosci. 2005 Oct 12;25(41):9378-83 PMID: 16221846
  3. First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients.
    Mol Psychiatry. 2006 Feb;11(2):118-9 PMID: 16189506
  4. Altered neuregulin 1-erbB4 signaling contributes to NMDA receptor hypofunction in schizophrenia.
    Nat Med. 2006 Jul;12(7):824-8 PMID: 16767099
  5. Schizophrenia genes - famine to feast.
    Biol Psychiatry. 2006 Jul 15;60(2):81-3 PMID: 16843093
  6. Further evidence for association between ErbB4 and schizophrenia and influence on cognitive intermediate phenotypes in healthy controls.
    Mol Psychiatry. 2006 Dec;11(12):1062-5 PMID: 17130882
  7. Translational and developmental perspective on N-methyl-D-aspartate synaptic deficits in schizophrenia.
    Dev Psychopathol. 2006 Summer;18(3):853-76 PMID: 17152404
  8. Modeling of context-dependent retrieval in hippocampal region CA1: implications for cognitive function in schizophrenia.
    Schizophr Res. 2007 Jan;89(1-3):177-90 PMID: 17055702
  9. Disease-associated intronic variants in the ErbB4 gene are related to altered ErbB4 splice-variant expression in the brain in schizophrenia.
    Hum Mol Genet. 2007 Jan 15;16(2):129-41 PMID: 17164265
  10. Neuregulin1 (NRG1) signaling through Fyn modulates NMDA receptor phosphorylation: differential synaptic function in NRG1+/- knock-outs compared with wild-type mice.
    J Neurosci. 2007 Apr 25;27(17):4519-29 PMID: 17460065
  11. The neuregulin-1 receptor erbB4 controls glutamatergic synapse maturation and plasticity.
    Neuron. 2007 May 24;54(4):583-97 PMID: 17521571
  12. Neuregulin-1 enhances depolarization-induced GABA release.
    Neuron. 2007 May 24;54(4):599-610 PMID: 17521572
  13. Developmental profile of neuregulin receptor ErbB4 in postnatal rat cerebral cortex and hippocampus.
    Neuroscience. 2007 Aug 10;148(1):126-39 PMID: 17630218
  14. The neuregulin receptor ErbB-4 interacts with PDZ-containing proteins at neuronal synapses.
    Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3596-601 PMID: 10725395
  15. Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses.
    Neuron. 2000 May;26(2):443-55 PMID: 10839362
  16. Ionotropic glutamate receptors and expression of N-methyl-D-aspartate receptor subunits in subregions of human hippocampus: effects of schizophrenia.
    Am J Psychiatry. 2000 Jul;157(7):1141-9 PMID: 10873924
  17. ErbB transmembrane tyrosine kinase receptors are differentially expressed throughout the adult rat central nervous system.
    J Comp Neurol. 2001 Apr 23;433(1):86-100 PMID: 11283951
  18. Theta returns.
    Curr Opin Neurobiol. 2001 Dec;11(6):739-44 PMID: 11741027
  19. Neural development of the neuregulin receptor ErbB4 in the cerebral cortex and the hippocampus: preferential expression by interneurons tangentially migrating from the ganglionic eminences.
    Cereb Cortex. 2003 Mar;13(3):252-64 PMID: 12571115
  20. Cognitive experimental approaches to investigating impaired cognition in schizophrenia: a paradigm shift.
    J Clin Exp Neuropsychol. 2002 Oct;24(7):873-82 PMID: 12647766
  21. Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality.
    Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8281-6 PMID: 12824469
  22. Converging evidence of NMDA receptor hypofunction in the pathophysiology of schizophrenia.
    Ann N Y Acad Sci. 2003 Nov;1003:318-27 PMID: 14684455
  23. Heregulin induces tyrosine phosphorylation of HER4/p180erbB4.
    Nature. 1993 Dec 2;366(6454):473-5 PMID: 7902537
  24. Tyrosine kinase inhibitors. 14. Structure-activity relationships for methylamino-substituted derivatives of 4-[(3-bromophenyl)amino]-6-(methylamino)-pyrido[3,4-d]pyrimidine (PD 158780), a potent and specific inhibitor of the tyrosine kinase activity of receptors for the EGF family of growth factors.
    J Med Chem. 1998 Feb 26;41(5):742-51 PMID: 9513602
  25. The involvement of ErbB4 with schizophrenia: association and expression studies.
    Am J Med Genet B Neuropsychiatr Genet. 2006 Mar 5;141B(2):142-8 PMID: 16402353
Article Info
Journal
Neuroreport
Abbr.
Neuroreport
ISSN
0959-4965
DOI
10.1097/WNR.0b013e3282f3da10
Email
[email protected]
Published
2008-01-22
Pages
139-43
Language
English
Region
England
NLM ID
9100935
PMCID
PMC3707840
Subset
IM
Grants
Canadian Institutes of Health Research · 12682-5 · Canada
External Links
PubMed source DOI: 10.1097/WNR.0b013e3282f3da10 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2