Neurobiologia Funcional y de Sistemas, Instituto Cajal, CSIC, Madrid 28002, Spain.
CIBERNED, ISCIII, Madrid 28002, Spain.
Cereb Cortex. 2021 Mar 5;31(4):2187-2204. doi: 10.1093/cercor/bhaa354.
Dopamine receptors play an important role in motivational, emotional, and motor responses. In addition, growing evidence suggests a key role of hippocampal dopamine receptors in learning and memory. It is well known that associative learning and synaptic plasticity of CA3-CA1 requires the dopamine D1 receptor (D1R). However, the specific role of the dopamine D2 receptor (D2R) on memory-related neuroplasticity processes is still undefined. Here, by using two models of D2R loss, D2R knockout mice (Drd2-/-) and mice with intrahippocampal injections of Drd2-small interfering RNA (Drd2-siRNA), we aimed to investigate how D2R is involved in learning and memory as well as in long-term potentiation of the hippocampus. Our studies revealed that the genetic inactivation of D2R impaired the spatial memory, associative learning, and the classical conditioning of eyelid responses. Similarly, deletion of D2R reduced the activity-dependent synaptic plasticity in the hippocampal CA1-CA3 synapse. Our results demonstrate the first direct evidence that D2R is essential in behaving mice for trace eye blink conditioning and associated changes in hippocampal synaptic strength. Taken together, these results indicate a key role of D2R in regulating hippocampal plasticity changes and, in consequence, acquisition and consolidation of spatial and associative forms of memory.
多巴胺受体在动机、情感和运动反应中发挥着重要作用。此外，越来越多的证据表明海马体多巴胺受体在学习和记忆中起着关键作用。众所周知，CA3-CA1 的联想学习和突触可塑性需要多巴胺 D1 受体（D1R）。然而，多巴胺 D2 受体（D2R）在与记忆相关的神经可塑性过程中的具体作用仍未确定。在这里，我们使用两种 D2R 缺失模型，即 D2R 敲除小鼠（Drd2-/-）和海马内注射 Drd2-siRNA 的小鼠，旨在研究 D2R 如何参与学习和记忆以及海马体的长时程增强。我们的研究表明，D2R 的遗传失活会损害空间记忆、联想学习和眨眼反应的经典条件反射。同样，D2R 的缺失减少了海马 CA1-CA3 突触中的活性依赖性突触可塑性。我们的结果首次直接证明 D2R 对于行为小鼠的痕迹眨眼条件反射以及海马体突触强度的相关变化是必不可少的。总之，这些结果表明 D2R 在调节海马体可塑性变化以及空间和联想形式记忆的获得和巩固方面起着关键作用。
