Abstract
Neuregulin-1 (NRG1), a regulator of neural development, has been shown to regulate neurotransmission at excitatory synapses. Although ErbB4, a key NRG1 receptor, is expressed in glutamic acid decarboxylase (GAD)-positive neurons, little is known about its role in GABAergic transmission. We show that ErbB4 is localized at GABAergic terminals of the prefrontal cortex. Our data indicate a role of NRG1, both endogenous and exogenous, in regulation of GABAergic transmission. This effect was blocked by inhibition or mutation of ErbB4, suggesting the involvement of ErbB4. Together, these results indicate that NRG1 regulates GABAergic transmission via presynaptic ErbB4 receptors, identifying a novel function of NRG1. Because both NRG1 and ErbB4 have emerged as susceptibility genes of schizophrenia, these observations may suggest a mechanism for abnormal GABAergic neurotransmission in this disorder.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Cells, Cultured
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Dose-Response Relationship, Drug
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Drug Interactions
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Enzyme Inhibitors / pharmacology
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ErbB Receptors / metabolism
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Glutamate Decarboxylase / metabolism
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Glutamic Acid / metabolism
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Green Fluorescent Proteins / metabolism
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Hippocampus / cytology
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In Situ Hybridization
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In Vitro Techniques
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Inhibitory Postsynaptic Potentials / drug effects
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Inhibitory Postsynaptic Potentials / physiology
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Inhibitory Postsynaptic Potentials / radiation effects
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Neuregulin-1 / metabolism*
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Neuregulin-1 / pharmacology*
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Neurons / cytology
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Neurons / drug effects*
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Neurons / physiology
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Neurons / radiation effects
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Patch-Clamp Techniques / methods
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Potassium Chloride / pharmacology
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Presynaptic Terminals / metabolism
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Rats
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Receptor, ErbB-4
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Transfection / methods
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gamma-Aminobutyric Acid / metabolism*
Substances
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Enzyme Inhibitors
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Neuregulin-1
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Green Fluorescent Proteins
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Glutamic Acid
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gamma-Aminobutyric Acid
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Potassium Chloride
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ErbB Receptors
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Erbb4 protein, rat
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Receptor, ErbB-4
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Glutamate Decarboxylase