Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Science. 2013 Jun 7;340(6137):1234-9. doi: 10.1126/science.1234733.
Although cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is correlated with obsessive compulsive disorder (OCD), causation cannot be tested in humans. We used optogenetics in mice to simulate CSTC hyperactivation observed in OCD patients. Whereas acute orbitofrontal cortex (OFC)-ventromedial striatum (VMS) stimulation did not produce repetitive behaviors, repeated hyperactivation over multiple days generated a progressive increase in grooming, a mouse behavior related to OCD. Increased grooming persisted for 2 weeks after stimulation cessation. The grooming increase was temporally coupled with a progressive increase in light-evoked firing of postsynaptic VMS cells. Both increased grooming and evoked firing were reversed by chronic fluoxetine, a first-line OCD treatment. Brief but repeated episodes of abnormal circuit activity may thus set the stage for the development of persistent psychopathology.
尽管皮质纹状体丘脑皮质（CSTC）回路失调与强迫症（OCD）相关，但在人类中无法进行因果关系的测试。我们使用光遗传学在小鼠中模拟了 OCD 患者中观察到的 CSTC 过度激活。虽然急性眶额皮层（OFC）-腹侧纹状体（VMS）刺激不会产生重复性行为，但多天的反复过度激活会导致梳理行为逐渐增加，这是一种与 OCD 相关的小鼠行为。刺激停止后，梳理行为的增加持续了 2 周。梳理行为的增加与光刺激后 VMS 细胞的诱发放电逐渐增加具有时间相关性。慢性氟西汀（一线 OCD 治疗药物）可逆转增加的梳理行为和诱发放电。因此，短暂但反复的异常回路活动可能会为持续性精神病理学的发展奠定基础。
