National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, 20892, USA.
National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, 20892, USA.
Mol Psychiatry. 2020 Feb;25(2):491-505. doi: 10.1038/s41380-018-0051-3. Epub 2018 Apr 25.
The dorsal striatum has been linked to decision-making under conflict, but the mechanism by which striatal neurons contribute to approach-avoidance conflicts remains unclear. We hypothesized that striatopallidal dopamine D2 receptor (D2R)-expressing neurons promote avoidance, and tested this hypothesis in two exploratory approach-avoidance conflict paradigms in mice: the elevated zero maze and open field. Genetic elimination of D2Rs on striatopallidal neurons (iMSNs), but not other neural populations, increased avoidance of the open areas in both tasks, in a manner that was dissociable from global changes in movement. Population calcium activity of dorsomedial iMSNs was disrupted in mice lacking D2Rs on iMSNs, suggesting that disrupted output of iMSNs contributes to heightened avoidance behavior. Consistently, artificial disruption of iMSN output with optogenetic stimulation heightened avoidance of open areas of these tasks, while inhibition of iMSN output reduced avoidance. We conclude that dorsomedial striatal iMSNs control approach-avoidance conflicts in exploratory tasks, and highlight this neural population as a potential target for reducing avoidance in anxiety disorders.
背侧纹状体与冲突下的决策有关，但纹状体神经元如何促成趋近-回避冲突仍不清楚。我们假设纹状苍白球多巴胺 D2 受体（D2R）表达神经元促进回避，并在小鼠的两个探索性趋近-回避冲突范式中检验了这一假设：高架零迷宫和开阔场。在这两种任务中，特异性消除纹状苍白球神经元（iMSNs）上的 D2R，而不是其他神经元群体，增加了对开阔区域的回避，这种方式与运动的整体变化无关。在缺乏 iMSNs 上的 D2R 的小鼠中，背内侧 iMSNs 的群体钙活性被破坏，这表明 iMSNs 输出的破坏导致回避行为增强。一致地，用光遗传学刺激人工破坏 iMSN 的输出会增加这些任务中对开阔区域的回避，而抑制 iMSN 的输出则会减少回避。我们得出结论，背侧纹状体 iMSNs 控制探索性任务中的趋近-回避冲突，并强调该神经元群体作为减少焦虑障碍中回避行为的潜在靶点。
