Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout mice.
Selective populations of hippocampal interneurons express ErbB4 and their number and distribution is altered in ErbB4 knockout mice.
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DOI：
10.1002/hipo.20675
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发表时间：
2010-06
期刊：
影响因子：
3.5
通讯作者：
Buonanno, Andres
中科院分区：
文献类型：
--
作者：
Neddens, Joerg;Buonanno, Andres
神经调节蛋白（NRG）是ErbB受体酪氨酸激酶的配体。NRG 1-ErbB 4通路已被证明可以调节成年啮齿动物脑中海马突触可塑性和网络振荡。为了鉴定介导这些效应的细胞，我们确定了ErbB 4在四种功能不同的中间神经元中的表达模式，这些中间神经元代表了海马中所有抑制性神经元的大多数。基于来自15只小鼠和25，000个细胞的数据，我们发现ErbB 4在胆囊收缩素（CCK，54%）、小清蛋白（PV，42%）或神经元型一氧化氮合酶（nNOS，39%）阳性的细胞中以层特异性和区域特异性方式表达，而表达生长抑素（SOM）的细胞很少对ErbB 4免疫反应（1%）。接下来，我们比较了ErbB 4 −/−小鼠和野生型对照之间中间神经元的数量密度（细胞/mm 3）和分布。基于25只小鼠和56，000个细胞的数据，我们检测到PV阳性和nNOS阳性细胞在敲除中减少（分别为-24%和-27%），但CCK阳性细胞仅轻微减少;未观察到SOM阳性细胞的变化。通过GAD 67免疫反应性细胞的定量（ErbB 4 −/−小鼠中为−24%）证实了中间神经元的总体减少。中间神经元沿着背腹轴的减少是更严重的中间和腹侧部分比背侧海马，和区域减少发生在CA 1 -3区和下托，而我们没有发现在齿状回的显着变化。不同群体的interneurons的表达表明，ErbB 4可以调节海马内的几个微电路，并介导先前报道的NRG 1对网络振荡和突触可塑性的影响。ErbB 4 −/−小鼠中GABA能细胞的选择性减少与NRG-ErbB 4信号在发育过程中中间神经元的产生和迁移中的作用以及成年ErbB 4敲除小鼠中的神经元和行为功能缺陷一致。
Neuregulins (NRGs) are ligands of ErbB receptor tyrosine kinases. The NRG1-ErbB4 pathway has been shown to modulate hippocampal synaptic plasticity and network oscillations in the adult rodent brain. In order to identify cells that mediate these effects here we determine the expression pattern of ErbB4 in four functionally distinct classes of interneurons that represent the majority of all inhibitory neurons in the hippocampus. Based on data from 15 mice and 25,000 cells, we show that ErbB4 is expressed in cells that are positive for cholecystokinin (CCK, 54%), parvalbumin (PV, 42%), or neuronal nitric oxide synthase (nNOS, 39%) in a layer-specific and region-specific manner, whereas cells expressing somatostatin (SOM) are rarely immunoreactive for ErbB4 (1%). We next compared the numerical density (cells/mm3) and the distribution of interneurons between ErbB4−/− mice and wildtype controls. Based on data from 25 mice and 56,000 cells, we detected reductions of PV-positive and nNOS-positive cells in knockouts (−24% and −27%, respectively) but only a minor reduction of CCK-positive cells; no changes in SOM-positive cells were observed. The overall reduction of interneurons was verified by quantification of GAD67-immunoreactive cells (−24% in ErbB4−/− mice). The reduction of interneurons along the dorsoventral axis was more severe in intermediate and ventral portions than in the dorsal hippocampus, and regional reductions occurred in the CA1-3 regions and subiculum, whereas we found no significant changes in the dentate gyrus. The expression by different populations of interneurons suggests that ErbB4 can modulate several microcircuits within the hippocampus and mediate the previously reported effects of NRG1 on network oscillations and synaptic plasticity. The selective reduction of GABAergic cells in ErbB4−/− mice is consistent with the role of NRG-ErbB4 signaling in the generation and migration of interneurons during development, and with neuronal and behavioral functional deficits in adult ErbB4 knockouts.
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影响因子：
16.2
作者：
Brinkmann, Bastian G.;Agarwal, Amit;Sereda, Michael W.;Garratt, Alistair N.;Mueller, Thomas;Wende, Hagen;Stassart, Ruth M.;Nawaz, Schanila;Humml, Christian;Velanac, Viktorija;Radyushkin, Konstantin;Goebbels, Sandra;Fischer, Tobias M.;Franklin, Robin J.;Lai, Cary;Ehrenreich, Hannelore;Birchmeier, Carmen;Schwab, Markus H.;Nave, Klaus Armin
通讯作者：
Nave, Klaus Armin
影响因子：
3.7
作者：
Baude, Agnes;Bleasdale, Catherine;Klausberger, Thomas
通讯作者：
Klausberger, Thomas
影响因子：
16.2
作者：
Flames, N;Long, JE;Marín, O
通讯作者：
Marín, O
影响因子：
3.3
作者：
Erlich, S;Goldshmit, Y;Pinkas-Kramarski, R
通讯作者：
Pinkas-Kramarski, R
影响因子：
3.1
作者：
Di Segni, Ayelet;Farin, Keren;Pinkas-Kramarski, Ronit
通讯作者：
Pinkas-Kramarski, Ronit