mGluR1 in cerebellar Purkinje cells is required for normal association of temporally contiguous stimuli in classical conditioning
mGluR1 in cerebellar Purkinje cells is required for normal association of temporally contiguous stimuli in classical conditioning
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DOI：
10.1046/j.1460-9568.2002.02407.x
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发表时间：
2002-12-01
影响因子：
3.4
通讯作者：
Kirino, Y
中科院分区：
文献类型：
--
作者：
Kishimoto, Y;Fujimichi, R;Kirino, Y
在代谢型谷氨酸受体亚型1（mGluR 1）-null（mGluR 1（-/-））小鼠中，小脑长期抑郁（LTD）和几种形式的记忆受损。然而，由于mGluR 1在野生型小鼠的不同脑区中表达，因此很难确定哪种类型的记忆依赖于特定脑区中表达的mGluR 1。此外，mGluR 1（-/-）小鼠的严重共济失调使非小脑依赖性任务的数据解释复杂化。我们通过将mGluR 1 α转基因引入到PC特异性启动子控制下的mGluR 1（-/-）小鼠中，产生了mGluR 1-rescue小鼠，其仅在小脑的浦肯野细胞（PC）中表达mGluR 1。mGluR 1-救援小鼠具有正常LTD，并且没有表现出明显的共济失调。因此，该小鼠是第一个可以在没有小脑功能障碍的情况下研究PC外mGluR 1缺乏影响的动物模型。我们使用了三种不同时间特异性的条件刺激（CS）和非条件刺激（US）之间的眨眼条件反射范式。延迟条件反射，其中CS和US共终止，在mGluR 1（-/-）小鼠受损，但在mGluR 1救援小鼠正常。然而，这两种品系的小鼠显示严重损害的痕迹条件，其中250或500毫秒的无刺激间隔CS和US之间的干预。我们还研究了食物偏好和新物体识别记忆测试的社会传播。在这些任务中，mGluR 1救援小鼠表现出正常的短期记忆，但长期记忆受损。我们的结论是，mGluR 1在PC是不可或缺的正常学习的关联时间连续的刺激在关联条件反射。相比之下，mGluR 1在其他类型的细胞是必要的关联不连续的刺激和长期记忆的形成，在非空间记忆依赖性学习。
In metabotropic glutamate receptor-subtype 1 (mGluR1)-null (mGluR1(-/-)) mice, cerebellar long-term depression (LTD) and several forms of memory are impaired. However, because mGluR1 is expressed in various brain regions in wild-type mice, it has been difficult to identify which type of memory depends on mGluR1 expressed in a given brain region. Furthermore, severe ataxia in mGluR1(-/-) mice complicated interpretation of the data from non-cerebellum-dependent tasks. We have generated mGluR1-rescue mice, which express mGluR1 only in Purkinje cells (PCs) of their cerebellum, by introducing the mGluR1alpha transgene into mGluR1(-/-) mice under the control of a PC-specific promoter. The mGluR1-rescue mouse has normal LTD and displays no apparent ataxia. Therefore, this mouse is the first animal model in which effects of mGluR1 deficiency outside PCs can be studied without cerebellar dysfunction. We used three eyeblink conditioning paradigms with different temporal specificities between conditioned stimulus (CS) and unconditioned stimulus (US). Delay conditioning, in which CS and US coterminate, was impaired in mGluR1(-/-) mice but normal in mGluR1-rescue mice. However, both strains of mice displayed severe impairment in trace conditionings, in which a stimulus-free interval of 250 or 500 ms intervened between CS and US. We also examined social transmission of food-preference and novel-object-recognition memory tests. In these tasks, mGluR1-rescue mice showed normal short-term but impaired long-term memory. We conclude that mGluR1 in PCs is indispensable for normal learning of association of temporally contiguous stimuli in associative conditioning. In contrast, mGluR1 in other cell types is required for associating discontiguous stimuli and long-term memory formation in nonspatial hippocampus-dependent learning.