RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; and.
RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Department of Biology and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139; andHoward Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139
Proc Natl Acad Sci U S A. 2014 Jun 3;111(22):8245-50. doi: 10.1073/pnas.1407395111. Epub 2014 May 19.
Activation of the hippocampal dopamine 1-class receptors (D1R and D5R) are implicated in contextual fear conditioning (CFC). However, the specific role of the D1R versus D5R in hippocampal dependent CFC has not been investigated. Generation of D1R- and D5R-specific in situ hybridization probes showed that D1R and D5R mRNA expression was greatest in the dentate gyrus (DG) of the hippocampus. To identify the role of each receptor in CFC we generated spatially restricted KO mice that lack either the D1R or D5R in DG granule cells. DG D1R KOs displayed significant fear memory deficits, whereas DG D5R KOs did not. Furthermore, D1R KOs but not D5R KOs, exhibited generalized fear between two similar but different contexts. In the familiar home cage context, c-Fos expression was relatively low in the DG of control mice, and it increased upon exposure to a novel context. This level of c-Fos expression in the DG did not further increase when a footshock was delivered in the novel context. In DG D1R KOs, DG c-Fos levels in the home cage was higher than that of the control mice, but it did not further increase upon exposure to a novel context and remained at the same level upon a shock delivery. In contrast, the levels of DG c-Fos expression was unaffected by the deletion of DG D5R neither in the home cage nor upon a shock delivery. These results suggest that DG D1Rs, but not D5Rs, contribute to the formation of distinct contextual representations of novel environments.
海马多巴胺 1 型受体 (D1R 和 D5R) 的激活被认为与情境恐惧条件反射 (CFC) 有关。然而，D1R 和 D5R 在海马依赖性 CFC 中的具体作用尚未被研究。生成 D1R 和 D5R 特异性原位杂交探针表明，D1R 和 D5R mRNA 的表达在海马齿状回 (DG) 中最高。为了确定每个受体在 CFC 中的作用，我们生成了空间受限的 KO 小鼠，这些小鼠在 DG 颗粒细胞中缺乏 D1R 或 D5R。DG D1R KO 显示出明显的恐惧记忆缺陷，而 DG D5R KO 则没有。此外，D1R KO 而不是 D5R KO ，表现出两种相似但不同的环境之间的普遍恐惧。在熟悉的家笼环境中，对照小鼠 DG 中的 c-Fos 表达相对较低，而在暴露于新环境时则增加。当在新环境中给予电击时，DG 中的 c-Fos 表达水平不会进一步增加。在 DG D1R KO 中，DG 中的 c-Fos 水平高于对照小鼠，但在暴露于新环境时不会进一步增加，并且在给予电击时保持相同水平。相比之下，DG D5R 的缺失既不会影响家笼中的 DG c-Fos 表达水平，也不会影响电击时的 DG c-Fos 表达水平。这些结果表明，DG D1Rs 而不是 D5Rs 有助于形成新环境的独特情境表征。
