Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components.
Type III neuregulin-1 is required for normal sensorimotor gating, memory-related behaviors, and corticostriatal circuit components.
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DOI：
10.1523/jneurosci.1815-08.2008
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发表时间：
2008-07-02
期刊：
影响因子：
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通讯作者：
Role LW
中科院分区：
文献类型：
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作者：
Chen YJ;Johnson MA;Lieberman MD;Goodchild RE;Schobel S;Lewandowski N;Rosoklija G;Liu RC;Gingrich JA;Small S;Moore H;Dwork AJ;Talmage DA;Role LW
Neuregulin-1（Nrg 1）/erbB信号调节神经元发育、迁移、髓鞘形成和突触维持。Nrg 1基因是精神分裂症易感基因。为了了解Nrg 1信号传导对成人大脑结构和行为的贡献，我们研究了III型Nrg 1表达的调节，并评估了III型Nrg 1亚型表达减少的影响。III型Nrg 1由不同于其他Nrg 1亚型的启动子转录，并且在成人脑中，在内侧前额叶皮质、腹侧海马和腹侧下托中表达，这些区域参与感觉运动门控和短期记忆的调节。III型Nrg 1（Nrg1tm1.1Lwr+/-）靶向破坏的成年杂合突变小鼠侧脑室扩大，下锥体神经元树突棘密度降低。III型Nrg 1杂合子小鼠的MRI成像显示内侧前额叶皮质和海马CA 1和下托区域的功能减退。III型Nrg 1杂合子小鼠在延迟交替记忆任务中的表现也受损，前脉冲抑制（PPI）也有缺陷。长期尼古丁治疗消除了III型Nrg 1杂合子小鼠及其野生型同窝小鼠之间PPI的差异。我们的研究结果表明，III型Nrg 1信号在维持皮质-纹状体成分，并在参与感觉运动门控和短期记忆的神经回路中的作用。
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 have 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 (Nrg1tm1.1Lwr+/-) have enlarged lateral ventricles and decreased dendritic spine density on subicular pyramidal neurons. MRI imaging of Type III Nrg1 heterozygous mice revealed hypo-function 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 cortico-striatal components, and in the neural circuits involved in sensorimotor gating and short term memory.