Integrative Analysis of Long-range Top-down Cortical Circuit for Attentional Behavior

注意力缺陷症状经常在精神疾病中观察到，但对注意力缺陷症状的了解有限 调节注意力行为的神经回路具有有限的病理生理学洞察力。先前在人类中的研究 和啮齿动物的研究表明，额叶皮层，尤其是前扣带皮层（ACC）， 在实施自上而下的注意力控制中的作用。然而，精确的神经回路机制介导 注意力在很大程度上仍然未知。这项研究的目的是确定特定的额叶皮质投射 调节注意力行为的自上而下控制的神经回路。保存的长距离额叶皮层- 皮质投射调节视皮质（维斯）对猕猴中基于注意力的任务中的视觉刺激的反应， 小鼠的光遗传学操作表明，该电路可以增强视觉辨别灵敏度。 注意缺陷多动障碍、精神分裂症和孤独症患者伴随视觉注意时维斯活动的不适当额叶调制 这些缺陷可能部分是由于直接长期预测功能障碍。然而，这个回路中的活动 在注意行为中从未被直接和具体地检查过，也没有被选择性地检查过。 被操纵来因果地改善注意力行为。在这里，我们将测试的假设，长期顶端- 从额叶皮层直接投射到感觉皮层的下行皮层回路协调时间动力学 在这些区域之间有效地调节注意力行为， 组合地（1）监测和（2）操纵小鼠特定回路内的神经活动的策略， 翻译触摸屏系统，以评估在自然的自由移动行为的注意力。在AIM1中，我们将 识别在注意力行为期间自上而下的回路何时被激活。在Aim2中，我们将自上而下地操作 调节注意力行为的皮层回路活动。在这里，我们将测试的假设，自上而下的皮层 回路协调ACC和维斯之间的时间动态以有效地调节注意行为。在 这项研究的完成，我们将建立一个强大的基础，自上而下的皮层的因果作用， 注意力行为的回路

Attention deficit symptoms are frequently observed in psychiatric disorders, yet finite understanding of the neural circuits mediating attentional behavior has limited pathophysiologic insight. Previous studies in humans and rodent demonstrate that the frontal cortex—especially the anterior cingulate cortex (ACC)— plays a key role in implementing a top-down control of attention. However, the precise neural circuit mechanisms mediating attention remain largely unknown. The goal of this study is to identify the specific frontal cortex projecting neural circuits that mediate top-down control of attentional behavior. Conserved long-range frontal cortico- cortical projections regulate visual cortex (VIS) responses to visual stimuli in attention based tasks in macaque, and optogenetic manipulation in mice shows that this circuit can enhance visual discrimination sensitivity. Improper frontal modulation of VIS activity in ADHD, schizophrenia, and autism accompanying visual attention deficits may be in part due to the dysfunction of direct long-range projections. However, activity in this circuit has never been directly and specifically examined during attentional behavior, nor has been selectively manipulated to causally improve attentional behavior. Here we will test the hypothesis that long-range top- down cortical circuits directly projecting from frontal cortex to sensory cortex coordinate temporal dynamics between these regions to effectively modulate attentional behavior by implementing an intersectional viral strategy to combinatorially (1) monitor and (2) manipulate neural activity within specific circuits of mice with a translation touchscreen system to assess attention during naturalistic freely moving behavior. In Aim1, we will identify when top-down circuits are activated during attentional behavior. In Aim2, we will manipulate top-down cortical circuit activity to modulate attentional behavior. Here, we will test the hypothesis that top-down cortical circuits coordinate temporal dynamics between ACC and VIS to effectively modulate attentional behavior. At the completion of this study, we will have established a strong basis for the causal role of top-down cortical circuit on attentional behavior.