Altered synaptic transmission at olfactory and vomeronasal nerve terminals in mice lacking N‐type calcium channel Cav2.2
Altered synaptic transmission at olfactory and vomeronasal nerve terminals in mice lacking N‐type calcium channel Cav2.2
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缺乏 N 型钙通道 Cav2.2 的小鼠嗅觉和犁鼻神经末梢的突触传递发生改变
DOI：
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发表时间：
2014
影响因子：
3.4
通讯作者：
F. Zufall
中科院分区：
文献类型：
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作者：
J. Weiss;M. Pyrski;P. Weissgerber;F. Zufall
我们研究了电压激活钙(Cav)通道在小鼠嗅觉和副嗅觉通路第一突触的第一神经末梢的突触传递中的作用。我们提供了N型Cav通道亚单位Cav2.2在这些突触的突触前递质释放中起核心作用的证据。突触Cav2.2免疫反应定位于主嗅球(MOB)和副嗅球(AOB)的肾小球神经纤维，并与突触前分子(如巴松管)共同定位。电压钳记录二尖瓣/簇状突触(M/T)感觉神经诱发的兴奋性突触后电流(EPSCs)，结合已建立的亚型特异性Cav通道毒素，发现N型通道在这些突触的递质释放中起主导作用，而L型、P/Q型和R型通道没有或仅有相对较小的贡献。在缺乏N型通道Cav2.2(α1B)亚单位的CacNA1b突变小鼠中，嗅神经诱发的M/T细胞EPSCs没有减少，而是变得对阻滞剂具有抵抗力，因此表明由于该突触上Cav2.2的缺失，Cav通道亚单位发生了重大重组和补偿。Cav2.2基因缺陷的小鼠还发现，Cav2.2对于双脉冲抑制MOB的M/T细胞中的嗅神经诱发的EPSCs是至关重要的，并且它们对AOB二尖瓣细胞的犁鼻神经诱发的EPSCs中的Cav2.2也是必不可少的。因此，Cacna1b功能丧失突变不太可能导致全身性嗅觉丧失，但在寻找导致嗅觉改变的突变方面，Cacna1b是一个强有力的候选基因，例如一般嗅觉敏感性的变化和对化学刺激的社会反应变化。
We investigated the role of voltage‐activated calcium (Cav) channels for synaptic transmission at mouse olfactory and vomeronasal nerve terminals at the first synapse of the main and accessory olfactory pathways, respectively. We provided evidence for a central role of the N‐type Cav channel subunit Cav2.2 in presynaptic transmitter release at these synapses. Striking Cav2.2 immunoreactivity was localised to the glomerular neuropil of the main olfactory bulb (MOB) and accessory olfactory bulb (AOB), and co‐localised with presynaptic molecules such as bassoon. Voltage‐clamp recordings of sensory nerve‐evoked, excitatory postsynaptic currents (EPSCs) in mitral/tufted (M/T) and superficial tufted cells of the MOB and mitral cells of the AOB, in combination with established subtype‐specific Cav channel toxins, indicated a predominant role of N‐type channels in transmitter release at these synapses, whereas L‐type, P/Q‐type, and R‐type channels had either no or only relatively minor contributions. In Cacna1b mutant mice lacking the Cav2.2 (α1B) subunit of N‐type channels, olfactory nerve‐evoked M/T cell EPSCs were not reduced but became blocker‐resistant, thus indicating a major reorganisation and compensation of Cav channel subunits as a result of the Cav2.2 deletion at this synapse. Cav2.2‐deficient mice also revealed that Cav2.2 was critically required for paired‐pulse depression of olfactory nerve‐evoked EPSCs in M/T cells of the MOB, and they demonstrated an essential requirement for Cav2.2 in vomeronasal nerve‐evoked EPSCs of AOB mitral cells. Thus, Cacna1b loss‐of‐function mutations are unlikely to cause general anosmia but Cacna1b emerges as a strong candidate in the search for mutations causing altered olfactory perception, such as changes in general olfactory sensitivity and altered social responses to chemostimuli.
影响因子：
64.8
作者：
Weiss, Jan;Pyrski, Martina;Jacobi, Eric;Bufe, Bernd;Willnecker, Vivienne;Schick, Bernhard;Zizzari, Philippe;Gossage, Samuel J.;Greer, Charles A.;Leinders-Zufall, Trese;Woods, C. Geoffrey;Wood, John N.;Zufall, Frank
通讯作者：
Zufall, Frank
影响因子：
2.9
作者：
Newcomb, R;Szoke, B;Miljanich, G
通讯作者：
Miljanich, G