Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant
Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant
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DOI：
10.1038/s41467-018-08168-9
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发表时间：
2019-01-15
影响因子：
16.6
通讯作者：
Duman, Ronald S.
中科院分区：
文献类型：
--
作者：
Hare, Brendan D.;Shinohara, Ryota;Duman, Ronald S.
内侧前额叶皮层（mPFC）功能受损导致抑郁症，新型速效抗抑郁药（如氯胺酮）产生的治疗反应是由mPFC活性介导的。mPFC包含多种类型的锥体细胞，但尚不清楚是否有特定的亚型介导氯胺酮的快速抗抑郁作用。在这里，我们测试了两种主要亚型，Drd1和Drd2多巴胺受体表达锥体神经元，发现激活mPFC中表达Drd1的锥体细胞产生快速和持久的抗抑郁和抗焦虑反应。相反，光刺激表达Drd2的锥体细胞在焦虑样和抑郁样测量中无效。Drd1活性的破坏也阻断了氯胺酮的快速抗抑郁作用。最后，我们表明，刺激的mPFC Drd1终端在BLA概括的躯体刺激的抗抑郁作用。这些发现有助于理解mPFC中的细胞靶神经元和参与快速抗抑郁反应的下游回路。
Impaired function in the medial prefrontal cortex (mPFC) contributes to depression, and the therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated by mPFC activity. The mPFC contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates the rapid antidepressant actions of ketamine. Here we tested two major subtypes, Drd1 and Drd2 dopamine receptor expressing pyramidal neurons and found that activating Drd1 expressing pyramidal cells in the mPFC produces rapid and long-lasting antidepressant and anxiolytic responses. In contrast, photostimulation of Drd2 expressing pyramidal cells was ineffective across anxiety-like and depression-like measures. Disruption of Drd1 activity also blocked the rapid antidepressant effects of ketamine. Finally, we demonstrate that stimulation of mPFC Drd1 terminals in the BLA recapitulates the antidepressant effects of somatic stimulation. These findings aid in understanding the cellular target neurons in the mPFC and the downstream circuitry involved in rapid antidepressant responses.