Compulsive behaviors have been associated with striatal hyperactivity. Parvalbumin-positive striatal interneurons (PVIs) in the striatum play a crucial role in regulating striatal activity and suppressing prepotent inappropriate actions. To investigate the potential role of striatal PVIs in regulating compulsive behaviors, we assessed excessive self-grooming—a behavioral metric of compulsive-like behavior—in male Sapap3 knockout mice (Sapap3-KO). Continuous optogenetic activation of PVIs in striatal areas receiving input from the lateral orbitofrontal cortex reduced self-grooming events in Sapap3-KO mice to wild-type levels. Aiming to shorten the critical time window for PVI recruitment, we then provided real-time closed-loop optogenetic stimulation of striatal PVIs, using a transient power increase in the 1–4 Hz frequency band in the orbitofrontal cortex as a predictive biomarker of grooming onsets. Targeted closed-loop stimulation at grooming onsets was as effective as continuous stimulation in reducing grooming events but required 87% less stimulation time, paving the way for adaptive stimulation therapeutic protocols.

强迫行为与纹状体过度活跃有关。纹状体中的小白蛋白阳性纹状体中间神经元（PVI）在调节纹状体活动和抑制优势不当行为方面发挥着至关重要的作用。为了研究纹状体 PVI 在调节强迫行为中的潜在作用，我们评估了雄性Sapap3敲除小鼠 ( Sapap3 -KO)的过度自我修饰（强迫性行为的行为指标） 。接收来自外侧眶额皮质输入的纹状体区域中的 PVI 的连续光遗传学激活将Sapap3 -KO 小鼠的自我修饰事件减少至野生型水平。为了缩短 PVI 募集的关键时间窗口，我们对纹状体 PVI 进行实时闭环光遗传学刺激，使用眶额皮质 1-4 Hz 频段的瞬时功率增加作为梳理行为开始的预测生物标志物。在梳理毛发开始时进行有针对性的闭环刺激在减少梳理行为方面与连续刺激一样有效，但所需的刺激时间减少了 87%，这为适应性刺激治疗方案铺平了道路。