Type III Neuregulin-1 Is Required for Normal Sensorimotor Gating, Memory-Related Behaviors, and Corticostriatal Circuit Components
| Autor: | Madeleine A. Johnson, David A. Talmage, Ruei-Che Liu, Ying-Jiun J. Chen, Holly Moore, Gorazd Rosoklija, Lorna W. Role, Andrew J. Dwork, Michael D. Lieberman, Scott A. Schobel, Jay A. Gingrich, Nicole M. Lewandowski, Rose E. Goodchild, Scott A. Small |
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| Rok vydání: | 2008 |
| Předmět: |
Heterozygote
Dendritic spine Neuregulin-1 Prefrontal Cortex Hippocampus Mice Transgenic Nerve Tissue Proteins Hippocampal formation Nervous System Malformations Article Mice Lateral ventricles Lateral Ventricles Neural Pathways mental disorders Animals Protein Isoforms Nicotinic Agonists Neuregulin 1 Promoter Regions Genetic Prefrontal cortex Prepulse inhibition Mice Knockout Memory Disorders biology General Neuroscience Subiculum Gene Expression Regulation Developmental Neural Inhibition Corpus Striatum Disease Models Animal Memory Short-Term nervous system Sensation Disorders biology.protein Atrophy Psychology Neuroscience |
| Zdroj: | Journal of Neuroscience. 28:6872-6883 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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