Document Detail

Neuregulin directly decreases voltage-gated sodium current in hippocampal ErbB4-expressing interneurons.
MedLine Citation:
PMID:  23035098     Owner:  NLM     Status:  MEDLINE    
The Neuregulin 1 (NRG1)/ErbB4 signaling pathway has been genetically and functionally implicated in the etiology underlying schizophrenia, and in the regulation of glutamatergic pyramidal neuron function and plasticity. However, ErbB4 receptors are expressed in subpopulations of GABAergic interneurons, but not in hippocampal or cortical pyramidal neurons, indicating that NRG1 effects on principal neurons are indirect. Consistent with these findings, NRG1 effects on hippocampal long-term potentiation at CA1 pyramidal neuron synapses in slices are mediated indirectly by dopamine. Here we studied whether NRG/ErbB signaling directly regulates interneuron intrinsic excitability by pharmacologically isolating ErbB4-expressing neurons in rat dissociated hippocampal cultures, which lack dopaminergic innervation. We found that NRG1 acutely attenuates ErbB4-expressing interneuron excitability by depolarizing the firing threshold; neurons treated with the pan-ErbB inhibitor PD158780 or negative for ErbB4 were unaffected. These effects of NRG1 are primarily attributable to decreased voltage-gated sodium channel activity, as current density was attenuated by ∼60%. In stark contrast, NRG1 had minor effects on whole-cell potassium currents. Our data reveal the direct actions of NRG1 signaling in ErbB4-expressing interneurons, and offer novel insight into how NRG1/ErbB4 signaling can impact hippocampal activity.
Megan J Janssen; Elias Leiva-Salcedo; Andres Buonanno
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  32     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-04     Completed Date:  2013-01-17     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13889-95     Citation Subset:  IM    
Section on Molecular Neurobiology, Program in Developmental Neuroscience, Eunice Shriver Kennedy National Institute of Child Health and Human Development, Bethesda, Maryland 20892, USA.
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MeSH Terms
Action Potentials
Cells, Cultured / metabolism
Hippocampus / cytology,  metabolism*
Interneurons / chemistry,  metabolism*
Ion Transport / drug effects,  physiology
Nerve Tissue Proteins / analysis,  antagonists & inhibitors,  physiology
Neuregulin-1 / pharmacology*,  physiology
Peptide Fragments / pharmacology
Protein Structure, Tertiary
Pyrimidines / pharmacology
Rats, Sprague-Dawley
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  physiology*
Sodium / metabolism
Voltage-Gated Sodium Channel Blockers / pharmacology*
Voltage-Gated Sodium Channels / physiology
Grant Support
Reg. No./Substance:
0/6-(methylamino)pyrido(3,4-d)pyrimidine; 0/NRG1 protein, human; 0/Nerve Tissue Proteins; 0/Neuregulin-1; 0/Nrg1 protein, rat; 0/Peptide Fragments; 0/Pyrimidines; 0/Voltage-Gated Sodium Channel Blockers; 0/Voltage-Gated Sodium Channels; 0/neuregulin beta; 7440-23-5/Sodium; EC, Epidermal Growth Factor; EC tyrosine-protein kinase erbB-4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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