Regulation of Spine Formation by ErbB4 in PV-Positive Interneurons
Regulation of Spine Formation by ErbB4 in PV-Positive Interneurons
复制标题
DOI：
10.1523/jneurosci.2090-13.2013
复制
发表时间：
2013-12
期刊：
影响因子：
--
通讯作者：
Dong-Min Yin;Xiang-Dong Sun;Jonathan C. Bean;Thiri W. Lin;Anupama Sathyamurthy;W. Xiong;T. Gao;Yong-jun Chen;L. Mei
中科院分区：
文献类型：
--
作者：
Dong-Min Yin;Xiang-Dong Sun;Jonathan C. Bean;Thiri W. Lin;Anupama Sathyamurthy;W. Xiong;T. Gao;Yong-jun Chen;L. Mei
营养因子神经调节蛋白1（Nrg 1）及其受体ErbB 4是精神分裂症的候选基因。NRG 1-ErbB 4信号被认为以细胞自主的方式调节棘的形成和功能。然而，最近的研究表明，ErbB 4的表达主要局限于GABA能中间神经元，在锥体细胞中非常低或不存在。在这里，我们产生和表征细胞类型特异性ErbB 4突变体和转基因小鼠。棘密度和兴奋性突触的数量没有改变，既不删除，也不过度表达的ErbB 4在锥体神经元。然而，PV-ErbB 4 −/−小鼠的棘密度和兴奋性突触数量减少，其中ErbB 4在小清蛋白阳性GABA能中间神经元中被选择性消融。同时，PV-ErbB 4 −/−小鼠的基础谷氨酸传输受损，但在锥体神经元中ErbB 4缺失或过表达的小鼠中则没有。我们的研究结果表明，在兴奋性神经元的棘形成的PV阳性中间神经元中的ErbB 4的作用。
The trophic factor neuregulin 1 (Nrg1) and its receptor ErbB4 are schizophrenia candidate genes. NRG1-ErbB4 signaling was thought to regulate spine formation and function in a cell-autonomous manner. Yet, recent studies indicate that ErbB4 expression is largely restricted to GABAergic interneurons and is very low or absent in pyramidal cells. Here, we generated and characterized cell type-specific ErbB4 mutant and transgenic mice. Spine density and the number of excitatory synapses were unaltered by neither deletion nor overexpression of ErbB4 in pyramidal neurons. However, spine density and excitatory synapse number were reduced in PV-ErbB4−/− mice where ErbB4 was selectively ablated in parvalbumin-positive GABAergic interneurons. Concurrently, basal glutamate transmission was impaired in PV-ErbB4−/− mice, but not in mice where ErbB4 was deleted or overexpressed in pyramidal neurons. Our results demonstrate a role of ErbB4 in PV-positive interneurons for spine formation in excitatory neurons.