Cited by 188Schizophrenia research and treatmentNeuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental Disorders

Type III Neuregulin-1 Is Required for Normal Sensorimotor Gating, Memory-Related Behaviors, and Corticostriatal Circuit Components

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Chen, Y.-J. J., Johnson, M. A., Lieberman, M. D., Goodchild, R. E., Schobel, S., Lewandowski, N., Rosoklija, G., Liu, R.-C. +6 more·2008·Journal of Neuroscience

Abstract

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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Crossref · 10.1523/jneurosci.1815-08.2008

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  • Both these mouse lines show spine morphological deficits together with schizophrenia-related behavioral phenotypes.

    “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]

  • NRG1 type III-deficient mice have reduced spine density in hippocampal neurons.

    “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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  1. Lewis DA Lieberman JA Catching up on schizophrenia: natural history and neurobiology Neuron 2000 28 325 334 11144342

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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)
Venue
Journal of Neuroscience
Published
2008-07-02
Volume
28
Issue
27
Pages
6872-6883
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
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
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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