ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
Neuregulin1 (NRG1) signaling through Fyn modulates NMDA receptor phosphorylation: differential synaptic function in NRG1+/- knock-outs compared with wild-type mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01600885 (The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects), which is not on this map. Cited by 101 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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The Effects of Ketamine and Guanfacine on Working Memory in Healthy Subjects
Who cites it
101 citing papers in PubMed, 173 citations in OpenAlex.
- VTA-forebrain connectivity moderates adaptive behavior.Brain structure & function · 2026Review
- Neuroplasticity Across the Autism-Schizophrenia Continuum.Biomedicines · 2025Review
- Multiple Roles for Neuregulins and Their v-Erb-B2 Avian Erythroblastic Leukemia Viral Oncogene Homolog Receptors in Neurodegenerative Disease Pathogenesis and Therapy.The American journal of pathology · 2025Review
- Nrg1 intracellular signaling regulates the development of interhemispheric callosal axons in mice.Life science alliance · 2024Article
- Synaptic plasticity in schizophrenia pathophysiology.IBRO neuroscience reports · 2023Article
- Mitochondrial DNA Deficiency and Supplementation inInternational journal of molecular sciences · 2023Article
- Synaptic plasticity in schizophrenia pathophysiology.IBRO neuroscience reports · 2022Article
- Presentation and integration of multiple signals that modulate oligodendrocyte lineage progression and myelination.Frontiers in cellular neuroscience · 2022Review
- NRG1 accelerates the forgetting of fear memories and facilitates the induction of long-term depression in adult mice.Psychopharmacology · 2021Article
- The Implication of STEP in Synaptic Plasticity and Cognitive Impairments in Alzheimer's Disease and Other Neurological Disorders.Frontiers in cell and developmental biology · 2021Review
- CRISPR/Cas9-mediated Knockout of the Neuropsychiatric Risk Gene KCTD13 Causes Developmental Deficits in Human Cortical Neurons Derived from Induced Pluripotent Stem Cells.Molecular neurobiology · 2020Article
- On the Modulatory Roles of Neuregulins/ErbB Signaling on Synaptic Plasticity.International journal of molecular sciences · 2019Review
- Potential synaptic plasticity-based Shenzhiling oral liquid for a SAD Mouse Model.Brain and behavior · 2019Article
- Neuregulin directed molecular mechanisms of visual cortical plasticity.The Journal of comparative neurology · 2019Review
- Can N-Methyl-D-Aspartate Receptor Hypofunction in Schizophrenia Be Localized to an Individual Cell Type?Frontiers in psychiatry · 2019Review
- Article
- Neuregulin 3 promotes excitatory synapse formation on hippocampal interneurons.The EMBO journal · 2018Article
- Inhibition of STEPMolecular psychiatry · 2018Article
- mGluR1-Dependent Long Term Depression in Rodent Midbrain Dopamine Neurons Is Regulated by Neuregulin 1/ErbB Signaling.Frontiers in molecular neuroscience · 2018Article
- Immediate Early Genes Anchor a Biological Pathway of Proteins Required for Memory Formation, Long-Term Depression and Risk for Schizophrenia.Frontiers in behavioral neuroscience · 2018Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously identified Neuregulin1 (NRG1) as a gene contributing to the risk of developing schizophrenia. Furthermore, we showed that NRG1+/- mutant mice display behavioral abnormalities that are reversed by clozapine, an atypical antipsychotic drug used for the treatment of schizophrenia. We now present evidence that ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4), the tyrosine kinase receptor for NRG1 in hippocampal neurons, interacts with two nonreceptor tyrosine kinases, Fyn and Pyk2 (proline-rich tyrosine kinase 2). NRG1 stimulation of cells expressing ErbB4 and Fyn leads to the association of Fyn with ErbB4 and consequent activation. Furthermore, we show that NRG1 signaling, through activation of Fyn and Pyk2 kinases, stimulates phosphorylation of Y1472 on the NR2B subunit of the NMDA receptor (NMDAR), a key regulatory site that modulates channel properties. NR2B Y1472 is hypophosphorylated in NRG1+/- mutant mice, and this defect can be reversed by clozapine at a dose that reverses their behavioral abnormalities. We also demonstrate that short-term synaptic plasticity is altered and theta-burst long-term potentiation is impaired in NRG1+/- mutant mice, and incubation of hippocampal slices from these mice with NRG1 reversed those effects. Attenuated NRG1 signaling through ErbB4 may contribute to the pathophysiology of schizophrenia through dysfunction of NMDAR modulation. Thus, our data support the glutamate hypothesis of schizophrenia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.