Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States.
Department of Genetics, Harvard Medical School, Boston, United States.
Elife. 2023 Apr 4;12:e78349. doi: 10.7554/eLife.78349.
Absence seizures are characterized by brief periods of unconsciousness accompanied by lapses in motor function that can occur hundreds of times throughout the day. Outside of these frequent moments of unconsciousness, approximately a third of people living with the disorder experience treatment-resistant attention impairments. Convergent evidence suggests prefrontal cortex (PFC) dysfunction may underlie attention impairments in affected patients. To examine this, we use a combination of slice physiology, fiber photometry, electrocorticography (ECoG), optogenetics, and behavior in the mouse model of absence epilepsy. Attention function was measured using a novel visual attention task where a light cue that varied in duration predicted the location of a food reward. In mice, we find altered parvalbumin interneuron (PVIN) output in the medial PFC (mPFC) in vitro and PVIN hypoactivity along with reductions in gamma power during cue presentation in vivo. This was associated with poorer attention performance in mice that could be rescued by gamma-frequency optogenetic stimulation of PVINs. This highlights cue-related PVIN activity as an important mechanism for attention and suggests PVINs may represent a therapeutic target for cognitive comorbidities in absence epilepsy.
失神发作的特征是短暂的意识丧失，伴有运动功能丧失，这种情况一天可能会发生数百次。除了这些频繁的无意识时刻，大约三分之一患有这种疾病的人会经历治疗抵抗的注意力障碍。汇集的证据表明，前额叶皮层（PFC）功能障碍可能是受影响患者注意力障碍的基础。为了研究这一点，我们在失神性癫痫的小鼠模型中结合使用切片生理学、光纤光度法、皮层电图（ECoG）、光遗传学和行为来研究。使用一种新的视觉注意力任务来测量注意力功能，在该任务中，持续时间不同的光提示预测食物奖励的位置。我们发现，在体外，内侧前额叶皮层（mPFC）中的副交感神经节神经元（PVIN）输出改变，并且在体内提示呈现期间 PVIN 活性降低，伽马功率降低。这与小鼠的注意力表现较差有关，而通过对 PVIN 进行伽马频带光遗传学刺激可以挽救这种情况。这凸显了与提示相关的 PVIN 活性作为注意力的重要机制，并表明 PVIN 可能是失神性癫痫认知共病的治疗靶点。
