Cooperation Between Hippocampal Somatostatin Receptor Subtypes 4 and 2: Functional Relevance in Interactive Memory Systems
Cooperation Between Hippocampal Somatostatin Receptor Subtypes 4 and 2: Functional Relevance in Interactive Memory Systems
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DOI：
10.1002/hipo.20680
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发表时间：
2010-01-01
期刊：
影响因子：
3.5
通讯作者：
Guillou, Jean-Louis
中科院分区：
文献类型：
--
作者：
Gastambide, Francois;Lepousez, Gabriel;Guillou, Jean-Louis
海马生长抑素（sst）受体亚型4（sst（4））通过减少基于海马的空间功能而增强纹状体依赖性行为来调节记忆的形成。SST（4）介导的对海马神经元活动的调节似乎依赖于与SST受体亚型2（SST（2））的竞争和合作相互作用。在此，我们在水迷宫实验中研究了sst（4）介导的对海马依赖性空间记忆和纹状体依赖性线索记忆的影响是否需要sst（2）受体的相互作用。通过海马内注射sst（4）激动剂L-803，087单独或与sst（2）激动剂（L-779，976或奥曲肽）联合，在小鼠中评估竞争。还在sst（2）敲除小鼠中测试了L-803，087的作用，以评估受体协同作用。最后，通过免疫组织化学分析海马子区域内的sst（2a）和sst（4）定位，并通过实时qPCR定量sst（2a）和sst（2b）的表达水平。注射1803，087的海马苷损害了空间记忆，但增强了线索记忆。后一种效应不仅在sst（2）基因敲除小鼠中丧失，而且在sst（2）激动剂存在下也丧失，而前一种效应不受sst（2）激动剂或基因缺失的影响。奥曲肽和L-779，976没有产生记忆效应，但在整个习得试验中降低了游泳速度，这表明刺激sst（2）会影响动机和/或焦虑。在齿状回（DG）和海马CA 1区分别检测到sst（2a）和sst（4），提示它们的功能相互作用不是通过直接受体偶联介导的。海马sst（2a）的表达是sst（2b）的36倍。可能的神经机制和功能意义的记忆系统之间的相互作用与应激引起的海马功能的变化进行了讨论。(C)2009威利-利斯公司
The hippocampal somatostatin (sst) receptor subtype 4 (sst(4)) modulates memory formation by diminishing hippocampus-based spatial function while enhancing striatum-dependent behaviors. sst(4)-mediated regulations on neuronal activity in the hippocampus appear to depend on both competitive and cooperative interactions with sst receptor subtype 2 (sst(2)). Here, we investigated whether interactions with sst(2) receptors are required for sst(4)-mediated effects on hippocampus-dependent spatial memory and striatum-dependent cued memory in a water maze paradigm. Competition was assessed in mice by intrahippocampal injections of the sst(4) agonist L-803,087 alone or combined with sst(2) agonists (L-779,976 or octreotide). Effects of L-803,087 were also tested in sst(2) knockout mice to assess for receptor cooperation. Finally, sst(2a), and sst(4) localizations within hippocampal subregions were analyzed by immunohistochemistry and expression levels of sst(2a) and sst(2b), were quantified by real-time qPCR. Hippocampal injections of 1803,087 impaired spatial memory but enhanced cued memory. The latter effect was lost not only in sst(2) knockout mice but also in the presence of sst(2) agonists, whereas the former effect remained unaffected by sst(2) agonists or gene deletion. Octreotide and L-779,976 did not yield memory effects but reduced swim velocity throughout the acquisition trials suggesting that stimulation of sst(2) affected motivation and/or anxiety. sst(2a) and sst(4) were respectively detected in the dentate gyrus (DG) and the CA1 subfield suggesting that their functional interactions are not mediated by direct receptor coupling. Hippocampus sst(2a) expression was 36-fold higher than sst(2b). Possible neural mechanisms and functional significances for interaction between memory systems in relationship with stress-induced changes in hippocampal functions are discussed. (C) 2009 Wiley-Liss, Inc.