The Neuregulin-1 Receptor ErbB4 Controls Glutamatergic Synapse Maturation and Plasticity

Li, Bo; Woo, Ran-Sook; Mei, Lin; Malinow, Roberto

doi:10.1016/j.neuron.2007.03.028

Cited by 354Neuroscience and Neuropharmacology ResearchSchizophrenia research and treatmentGenetics and Neurodevelopmental Disorders

The Neuregulin-1 Receptor ErbB4 Controls Glutamatergic Synapse Maturation and Plasticity

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Li, Bo, Woo, Ran-Sook, Mei, Lin, Malinow, Roberto·2007·Neuron

DOI 10.1016/j.neuron.2007.03.028PMC PMC2031848

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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.

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ErbB4 overexpression increases spine density, area, and excitatory synaptic transmission.
“ErbB4 overexpression increases spine density, area and excitatory synaptic transmission49.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [49]
erbB4 knockdown reduces spine density and size in a cell-autonomous manner.
“Conversely, erbB4 knockdown reduces spine density and size in a cell-autonomous fashion49.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [49]
Neuregulin helps assemble both α-nicotinic and N-methyl-D-aspartate-type glutamate receptors.
“Neuregulin helps assemble both α-nicotinic and N-methyl-D-aspartate-type glutamate receptors (NMDARs) (30)”
From Sensory Processing Dysfunction in the Personal Experience and Neuronal Machinery of Schizophrenia (2015) · cites this paper as [30]

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Ozaki, M., Tohyama, K., Kishida, H., Buonanno, A., Yano, R., and Hashikawa, T. (2000). Roles of neuregulin in synaptogenesis between mossy fibers and cerebellar granule cells. J. Neurosci. Res. 59, 612- 623. 596 Neuron 54, 583-597, May 24, 2007 ª2007 Elsevier Inc. Neuron ErbB4 Controls Synapse Maturation and Plasticity

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Authors: Li, B., Woo, R.-S., Mei, L., & Malinow, R.
Affiliations: Cold Spring Harbor Laboratory (US)
Augusta University (US)
Corresponding author: Malinow, Roberto
ORCID: Li, Bo
Woo, Ran-Sook
Mei, Lin
Malinow, Roberto
Venue: Neuron
Publisher: Elsevier BV
Published: 2007-05
Volume: 54
Issue: 4
Pages: 583-597
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2007.03.028
PMC: PMC2031848
OpenAlex: W1980073907
Cited by: 354
References: 101
Citations by year: 2026: 7 · 2025: 6 · 2024: 11 · 2023: 12 · 2022: 10 · 2021: 12 · 2020: 14 · 2019: 14 · 2018: 12 · 2017: 16 · 2016: 12 · 2015: 19 · 2014: 22 · 2013: 17 · 2012: 19
FWCI: 14.42
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2305 d)
doi.org/10.15223/policy-017 (stm-asf)
doi.org/10.15223/policy-037 (stm-asf)
doi.org/10.15223/policy-012 (stm-asf)
doi.org/10.15223/policy-029 (stm-asf)
doi.org/10.15223/policy-004 (stm-asf)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders: National Institutes of Health
University of California, San Diego
National Institute on Aging (R01AG032132)
National Institute of Mental Health (R01MH049159, R37MH049159)
National Institute of Neurological Disorders and Stroke (R01NS032827)
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, synaptic plasticity, schizophrenia, AMPA receptors, NMDA currents, dendritic spines, neurodevelopmental deficits
MeSH terms: Animals, Animals, Newborn, Drug Interactions, Enzyme Inhibitors, Hippocampus, Synaptic Transmission, Neuronal Plasticity, Neurons, Quinazolines, Synapses, Transfection, N-Methylaspartate, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid, Patch-Clamp Techniques, Microscopy, Confocal, Glutamic Acid, Excitatory Postsynaptic Potentials, Tyrphostins, Neuregulin-1, RNA Interference, RNA, Small Interfering, Rats, ErbB Receptors, Receptor, ErbB-4, In Vitro Techniques

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The Neuregulin-1 Receptor ErbB4 Controls Glutamatergic Synapse Maturation and Plasticity

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