Tran Anh Hai, Uwano Teruko, Kimura Tatsuo, Hori Etsuro, Katsuki Motoya, Nishijo Hisao, Ono Taketoshi
System Emotional Science, University of Toyama, Toyama 930-0194, Japan.
J Neurosci. 2008 Dec 10;28(50):13390-400. doi: 10.1523/JNEUROSCI.2680-08.2008.
The human hippocampus is critical for learning and memory. In rodents, hippocampal pyramidal neurons fire in a location-specific manner, forming relational representations of environmental cues. The importance of glutamatergic systems in learning and in hippocampal neural synaptic plasticity has been shown. However, the role of dopaminergic systems in the response of hippocampal neural plasticity to novel and familiar spatial stimuli remains unclear. To clarify this important issue, we recorded hippocampal neurons from dopamine D(1) receptor knock-out (D1R-KO) mice and their wild-type (WT) littermates under the manipulation of distinct spatial cues in a familiar and a novel environment. Here we report that in WT mice, the majority of place cells quickly responded to the manipulations of distal and proximal cues in both familiar and novel environments. In contrast, the influence of distal cues on spatial firing in D1R-KO mice was abolished. In the D1R-KO mice, the influence of proximal cues was facilitated in a familiar environment, and in a novel environment most of the place cells were less likely to respond to changes of spatial cues. Our results demonstrate that hippocampal neurons in mice can rapidly and flexibly encode information about space from both distal and proximal cues to cipher a novel environment. This ability is necessary for many types of learning, and lacking D1R can radically alter this learning-related neural activity. We propose that D1R is crucially implicated in encoding spatial information in novel environments, and influences the plasticity of hippocampal representations, which is important in spatial learning and memory.
人类海马体对学习和记忆至关重要。在啮齿动物中，海马体锥体细胞以位置特异性方式放电，形成环境线索的关系表征。谷氨酸能系统在学习和海马体神经突触可塑性中的重要性已得到证实。然而，多巴胺能系统在海马体神经可塑性对新的和熟悉的空间刺激的反应中的作用仍不清楚。为了阐明这一重要问题，我们在熟悉和新的环境中通过不同空间线索的操纵，记录了多巴胺D(1)受体敲除（D1R-KO）小鼠及其野生型（WT）同窝小鼠的海马体神经元。在此我们报告，在WT小鼠中，大多数位置细胞在熟悉和新的环境中都能快速对远端和近端线索的操纵做出反应。相比之下，远端线索对D1R-KO小鼠空间放电的影响被消除。在D1R-KO小鼠中，近端线索在熟悉环境中的影响得到促进，而在新环境中大多数位置细胞对空间线索变化做出反应的可能性较小。我们的结果表明，小鼠海马体神经元可以快速灵活地从远端和近端线索中编码有关空间的信息，以破解新环境。这种能力对许多类型的学习都是必要的，而缺乏D1R会从根本上改变这种与学习相关的神经活动。我们提出，D1R在新环境中编码空间信息方面至关重要，并影响海马体表征的可塑性，这在空间学习和记忆中很重要。
