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Type III Neuregulin-1 Is Required for Normal Sensorimotor Gating, Memory-Related Behaviors, and Corticostriatal Circuit Components
Open accessAbstract
Neuregulin-1 (Nrg1)/erbB signaling regulates neuronal development, migration, myelination, and synaptic maintenance. The Nrg1 gene is a schizophrenia susceptibility gene. To understand the contribution of Nrg1 signaling to adult brain structure and behaviors, we studied the regulation of type III Nrg1 expression and evaluated the effect of decreased expression of the type III Nrg1 isoforms. Type III Nrg1 is transcribed by a promoter distinct from those for other Nrg1 isoforms and, in the adult brain, is expressed in the medial prefrontal cortex, ventral hippocampus, and ventral subiculum, regions involved in the regulation of sensorimotor gating and short-term memory. Adult heterozygous mutant mice with a targeted disruption for type III Nrg1 (Nrg1(tm1.1Lwr+/-)) have enlarged lateral ventricles and decreased dendritic spine density on subicular pyramidal neurons. Magnetic resonance imaging of type III Nrg1 heterozygous mice revealed hypofunction in the medial prefrontal cortex and the hippocampal CA1 and subiculum regions. Type III Nrg1 heterozygous mice also have impaired performance on delayed alternation memory tasks, and deficits in prepulse inhibition (PPI). Chronic nicotine treatment eliminated differences in PPI between type III Nrg1 heterozygous mice and their wild-type littermates. Our findings demonstrate a role of type III Nrg1 signaling in the maintenance of corticostriatal components and in the neural circuits involved in sensorimotor gating and short-term memory.
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“In both of these mouse lines, spine morphological deficits co-occur with schizophrenia-related behavioral phenotypes.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [89]
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“Mice deficient in NRG1 type III show reductions in spine density in hippocampal neurons89.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [89]
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“Long-term NRG1 treatment increases pyramidal neuronal spine density and the preponderance of spines with mature phenotypes [84] and mice deficient in NRG1 (type III) show reductions in spine density in hippocampal neurons [85].”
Background
Metadata
- Authors
- Chen, Y.-J. J., Johnson, M. A., Lieberman, M. D., Goodchild, R. E., Schobel, S., Lewandowski, N., Rosoklija, G., Liu, R.-C., Gingrich, J. A., Small, S., Moore, H., Dwork, A. J., Talmage, D. A., & Role, L. W.
- Affiliations
- Columbia University (US)
- University of California, San Francisco (US)
- New York State Psychiatric Institute (US)
- ORCID
- Venue
- Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-07-02
- Volume
- 28
- Issue
- 27
- Pages
- 6872-6883
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2728592
- OpenAlex
- W2074078151
- Cited by
- 188
- References
- 99
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 4 · 2018: 9 · 2017: 16 · 2016: 4 · 2015: 13 · 2014: 23 · 2013: 16 · 2012: 19
- FWCI
- 16.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institutes of Health (5p50mh066171-05)
- National Institute of Mental Health (R01MH064168, P50-MH066171, P50 MH66171-01, L30 MH075110)
- National Institute on Drug Abuse (DA019941, R21DA019941)
- National Institute of Neurological Disorders and Stroke (NS29071, R01NS029071)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- neuregulin-1, ErbB signaling, sensorimotor gating, prepulse inhibition, short-term memory, corticostriatal circuits, medial prefrontal cortex, hippocampus, ventral subiculum, dendritic spine density, lateral ventricle enlargement, schizophrenia risk genes, nicotine, heterozygous mutant mice
- MeSH terms
- Animals, Atrophy, Corpus Striatum, Disease Models, Animal, Heterozygote, Hippocampus, Memory Disorders, Memory, Short-Term, Mice, Transgenic, Nerve Tissue Proteins, Nervous System Malformations, Neural Inhibition, Neural Pathways, Promoter Regions, Genetic, Sensation Disorders, Prefrontal Cortex, Mice, Knockout, Gene Expression Regulation, Developmental, Nicotinic Agonists, Protein Isoforms, Lateral Ventricles, Neuregulin-1, Mice
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