Department of Neurology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany.
Institute of Pharmacology, Medical University of Innsbruck, 6020 Innsbruck, Austria.
Int J Mol Sci. 2021 Jul 22;22(15):7826. doi: 10.3390/ijms22157826.
The metabotropic glutamate receptor type 5 (mGluR5) has been proposed to play a crucial role in the selection and regulation of cognitive, affective, and emotional behaviors. However, the mechanisms by which these receptors mediate these effects remain largely unexplored. Here, we studied the role of mGluR5 located in D1 receptor-expressing (D1) neurons in the manifestation of different behavioral expressions. Mice with conditional knockout (cKO) of mGluR5 in D1 neurons (mGluR5 cKO) and littermate controls displayed similar phenotypical profiles in relation to memory expression, anxiety, and social behaviors. However, mGluR5 cKO mice presented different coping mechanisms in response to acute escapable or inescapable stress. mGluR5 cKO mice adopted an enhanced active stress coping strategy upon exposure to escapable stress in the two-way active avoidance (TWA) task and a greater passive strategy upon exposure to inescapable stress in the forced swim test (FST). In summary, this work provides evidence for a functional integration of the dopaminergic and glutamatergic system to mediate control over internal states upon stress exposure and directly implicates D1 neurons and mGluR5 as crucial mediators of behavioral stress responses.
代谢型谷氨酸受体 5（mGluR5）被认为在认知、情感和情绪行为的选择和调节中发挥关键作用。然而，这些受体介导这些效应的机制在很大程度上仍未得到探索。在这里，我们研究了位于 D1 受体表达（D1）神经元中的 mGluR5 在不同行为表现中的作用。D1 神经元中条件性敲除 mGluR5（mGluR5 cKO）的小鼠与同窝对照小鼠在记忆表达、焦虑和社交行为方面表现出相似的表型特征。然而，mGluR5 cKO 小鼠在应对急性可逃避或不可逃避应激时表现出不同的应对机制。mGluR5 cKO 小鼠在双路主动回避（TWA）任务中暴露于可逃避应激时采用增强的主动应激应对策略，而在强迫游泳试验（FST）中暴露于不可逃避应激时采用更大的被动策略。总之，这项工作为多巴胺能和谷氨酸能系统的功能整合提供了证据，以介导应激暴露时对内状态的控制，并直接表明 D1 神经元和 mGluR5 是行为应激反应的关键介导者。
