Li, B., Woo, R. S., Mei, L., Malinow, R. (May 2007) The Neuregulin-1 Receptor ErbB4 Controls Glutamatergic Synapse Maturation and Plasticity. Neuron, 54 (4). pp. 583-97. ISSN 0896-6273
Abstract
Neuregulin-1 (NRG1) signaling participates in numerous neurodevelopmental processes. Through linkage analysis, nrg1 has been associated with schizophrenia, although its pathophysiological role is not understood. The prevailing models of schizophrenia invoke hypofunction of the glutamatergic synapse and defects in early development of hippocampal-cortical circuitry. Here, we show that the erbB4 receptor, as a postsynaptic target of NRG1, plays a key role in activity-dependent maturation and plasticity of excitatory synaptic structure and function. Synaptic activity leads to the activation and recruitment of erbB4 into the synapse. Overexpressed erbB4 selectively enhances AMPA synaptic currents and increases dendritic spine size. Preventing NRG1/erbB4 signaling destabilizes synaptic AMPA receptors and leads to loss of synaptic NMDA currents and spines. Our results indicate that normal activity-driven glutamatergic synapse development is impaired by genetic deficits in NRG1/erbB4 signaling leading to glutamatergic hypofunction. These findings link proposed effectors in schizophrenia: NRG1/erbB4 signaling perturbation, neurodevelopmental deficit, and glutamatergic hypofunction.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | Animals Animals, Newborn Drug Interactions Enzyme Inhibitors/pharmacology Excitatory Postsynaptic Potentials/drug effects/physiology/radiation effects Glutamic Acid/ metabolism Hippocampus/cytology Microscopy, Confocal/methods N-Methylaspartate/pharmacology Neuregulin-1/genetics/metabolism Neuronal Plasticity/ physiology Neurons/ cytology Patch-Clamp Techniques/methods RNA Interference RNA, Small Interfering/pharmacology Rats Receptor, Epidermal Growth Factor/genetics/ physiology Synapses/ physiology Synaptic Transmission/drug effects/physiology/radiation effects Transfection/methods Tyrphostins/pharmacology alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi diseases & disorders > mental disorders > schizophrenia organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse |
| CSHL Authors: | |
| Communities: | CSHL labs > Li lab CSHL labs > Malinow lab |
| Depositing User: | CSHL Librarian |
| Date: | 24 May 2007 |
| Date Deposited: | 11 Nov 2011 14:50 |
| Last Modified: | 12 Dec 2014 19:52 |
| PMCID: | PMC2031848 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/23079 |
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