ArticleNature communications2015
A negative feedback loop controls NMDA receptor function in cortical interneurons via neuregulin 2/ErbB4 signalling.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 59 citations in OpenAlex.
- Chronic Overexpression of Neuronal NRG1-III in Mice Causes Long-Term Detrimental Changes in Lower Motor Neurons, Neuromuscular Synapses and Motor Behaviour.International journal of molecular sciences · 2025Article
- 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
- Exploration of schizophrenia-related behavioral and molecular abnormalities in a mutant mouse model with a mutation in the TVV motif of the ErbB4 gene.Molecular brain · 2025Article
- A Hidden Mark of a Troubled Past: Neuroimaging and Transcriptomic Analyses Reveal Interactive Effects of Maternal Immune Activation and Adolescent THC Exposure Suggestive of Increased Neuropsychiatric Risk.Biological psychiatry global open science · 2025Article
- Calcium channel signalling at neuronal endoplasmic reticulum-plasma membrane junctions.Biochemical Society transactions · 2024Review
- Neuregulin 2 Is a Candidate Gene for Autism Spectrum Disorder.International journal of molecular sciences · 2024Article
- Spatially resolved single-cell atlas of ascidian endostyle provides insight into the origin of vertebrate pharyngeal organs.Science advances · 2024Article
- Distinct cellular expression and subcellular localization of Kv2 voltage-gated KThe Journal of comparative neurology · 2024Article
- Distinct cellular expression and subcellular localization of Kv2 voltage-gated KbioRxiv : the preprint server for biology · 2023Article
- Neuregulin4 Acts on Hypothalamic ErBb4 to Excite Oxytocin Neurons and Preserve Metabolic Homeostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- ER-PM Junctions on GABAergic Interneurons Are Organized by Neuregulin 2/VAP Interactions and Regulated by NMDA Receptors.International journal of molecular sciences · 2023Article
- N-methyl-D-aspartate receptor hypofunction as a potential contributor to the progression and manifestation of many neurological disorders.Frontiers in molecular neuroscience · 2023Review
- Pathway-specific contribution of parvalbumin interneuron NMDARs to synaptic currents and thalamocortical feedforward inhibition.Molecular psychiatry · 2022Article
- Transcytosis and trans-synaptic retention by postsynaptic ErbB4 underlie axonal accumulation of NRG3.The Journal of cell biology · 2022Article
- Developmental, neurochemical, and behavioral analyses of ErbB4 Cyt-1 knockout mice.Journal of neurochemistry · 2022Article
- Alterations in prefrontal cortical neuregulin-1 levels in post-pubertal rats with neonatal ventral hippocampal lesions.Frontiers in behavioral neuroscience · 2022Article
- Location, location, location: the organization and roles of potassium channels in mammalian motoneurons.The Journal of physiology · 2021Article
- Neuregulins in Neurodegenerative Diseases.Frontiers in aging neuroscience · 2021Article
- Neuregulins 1, 2, and 3 Promote Early Neurite Outgrowth in ErbB4-Expressing Cortical GABAergic Interneurons.Molecular neurobiology · 2020Article
- Neuregulin 1: an intriguing therapeutic target for neurodevelopmental disorders.Translational psychiatry · 2020Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The neuregulin receptor ErbB4 is an important modulator of GABAergic interneurons and neural network synchronization. However, little is known about the endogenous ligands that engage ErbB4, the neural processes that activate them or their direct downstream targets. Here we demonstrate, in cultured neurons and in acute slices, that the NMDA receptor is both effector and target of neuregulin 2 (NRG2)/ErbB4 signalling in cortical interneurons. Interneurons co-express ErbB4 and NRG2, and pro-NRG2 accumulates on cell bodies atop subsurface cisternae. NMDA receptor activation rapidly triggers shedding of the signalling-competent NRG2 extracellular domain. In turn, NRG2 promotes ErbB4 association with GluN2B-containing NMDA receptors, followed by rapid internalization of surface receptors and potent downregulation of NMDA but not AMPA receptor currents. These effects occur selectively in ErbB4-positive interneurons and not in ErbB4-negative pyramidal neurons. Our findings reveal an intimate reciprocal relationship between ErbB4 and NMDA receptors with possible implications for the modulation of cortical microcircuits associated with cognitive deficits in psychiatric disorders.
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Registered trials
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.