Interactions of the mGluR5 gene with breeding and maternal factors on startle and prepulse inhibition in mice
Interactions of the mGluR5 gene with breeding and maternal factors on startle and prepulse inhibition in mice
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DOI：
10.1007/bf03033300
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发表时间：
2004-01-01
影响因子：
3.7
通讯作者：
Geyer, MA
中科院分区：
文献类型：
--
作者：
Brody, SA;Geyer, MA
通过脉冲前抑制（PPI）测量的感觉运动门控是一种基本的信息处理形式，在精神分裂症患者和缺乏代谢性谷氨酸受体5 （mGluR5）基因的小鼠中是缺乏的。育种策略和母性行为都能影响基因敲除（KO）小鼠的行为表型。先前的研究发现纯合子配对的mGluR5 KO小鼠存在PPI缺陷和惊吓程度增加。在这里，我们比较了mGluR5野生型（WT）和来自杂合交配的KO小鼠与来自纯合交配的小鼠的PPI。采用两种不同的交叉养育方法，探讨了产后育儿行为的可能影响。mGluR5 KO小鼠PPI缺陷的潜在发育性质也通过对C57BL/6J小鼠急性给予mGluR5拮抗剂2-甲基-6-（苯乙基）吡啶（MPEP）来解决。mGluR5 KO小鼠PPI下降与繁殖策略或产后母性行为无关。然而，惊吓程度因繁殖策略而异。在mGluR5 KO小鼠中观察到的PPI缺陷不会被急性给予mGluR5拮抗剂所模仿，因此最有可能是由于在发育过程中发生的神经元回路的代偿性改变，而不依赖于出生后环境中母亲的行为。
Sensorimotor gating, measured by prepulse inhibition (PPI), is a fundamental form of information processing that is deficient in schizophrenia patients and mice lacking the gene for metabotropic glutamate receptor 5 (mGluR5). Both breeding strategies and mothering behaviors are capable of influencing the behavioral phenotype of knockout (KO) mice. Previous studies found a PPI deficit and increased startle magnitudes in mGluR5 KO mice derived from homozygous matings. Here we compared the PPI of mGluR5 wildtype (WT) and KO mice derived from heterozygous matings to that seen in mice derived from homozygous matings. Possible influences of postnatal mothering behaviors were examined using two different methods of cross-fostering. The potential developmental nature of the PPI deficit of the mGluR5 KO mice was also addressed via acute administration of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) to C57BL/6J mice. The mGluR5 KO mice exhibited reduced PPI independently of breeding strategy or postnatal mothering behavior. Startle magnitude, however, varied with breeding strategy. The PPI deficit seen in the mGluR5 KO mice is not mimicked by acute administration of an mGluR5 antagonist, and is therefore most likely due to compensatory alterations in neuronal circuitry occurring during development independent of maternal behaviors in the postnatal environment.