D1 receptors in the anterior cingulate cortex modulate basal mechanical sensitivity threshold and glutamatergic synaptic transmission
D1 receptors in the anterior cingulate cortex modulate basal mechanical sensitivity threshold and glutamatergic synaptic transmission
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DOI：
10.1186/s13041-020-00661-x
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发表时间：
2020-09-05
期刊：
影响因子：
3.6
通讯作者：
Martin, Loren J.
中科院分区：
文献类型：
--
作者：
Darvish-Ghane, Soroush;Quintana, Clementine;Martin, Loren J.
多巴胺（DA）释放到靶脑区被认为是调节许多生理效应的重要事件。虽然前扣带皮层（ACC）已被牵连在疼痛相关的行为过程中，DA调制的ACC和疼痛相关的表型内的突触传递仍然不清楚。在这里，我们表征了Crispr/Cas9介导的ACC所有神经元亚型中D1受体（D1 R）的体细胞敲除，并发现机械阈值降低，而不影响运动和焦虑。此外，D1 R高效激动剂SKF 81297和低效激动剂（+/-）-SKF-38393抑制ACC中的α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）电流。有趣的是，D1 R拮抗剂SCH-23390和SCH 33961当与D1 R激动剂共同应用时，在ACC中产生对AMPAR电流的强烈短期协同抑制，证明了D1 R配体的总体抑制作用。总体而言，我们的数据表明，在ACC中的D1 R的缺乏增强外周对机械刺激的敏感性和D1 R的激活减少了ACC神经元的突触传递。
The release of dopamine (DA) into target brain areas is considered an essential event for the modulation of many physiological effects. While the anterior cingulate cortex (ACC) has been implicated in pain related behavioral processes, DA modulation of synaptic transmission within the ACC and pain related phenotypes remains unclear. Here we characterized a Crispr/Cas9 mediated somatic knockout of the D1 receptor (D1R) in all neuronal subtypes of the ACC and find reduced mechanical thresholds, without affecting locomotion and anxiety. Further, the D1R high-efficacy agonist SKF 81297 and low efficacy agonist (+/-)-SKF-38393 inhibit alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) currents in the ACC. Paradoxically, the D1R antagonists SCH-23390 and SCH 33961 when co-applied with D1R agonists produced a robust short-term synergistic depression of AMPAR currents in the ACC, demonstrating an overall inhibitory role for D1R ligands. Overall, our data indicate that absence of D1Rs in the ACC enhanced peripheral sensitivity to mechanical stimuli and D1R activation decreased glutamatergic synaptic transmission in ACC neurons.