Determining the neurons and neuromodulatory pathways underlying the prefrontal control of visual signals

注意是指我们将注意力集中在与行为相关的信息上，选择并增强一部分感官信息进行进一步处理，而忽略其余的信息。几十年的研究表明，前额叶皮层（PFC）与注意力控制有关。先前的研究表明，在PFC的额叶视野（FEF）部分，DA介导的活动的操纵增强了视觉区域的信号强度，提出了前额叶对注意力的控制是由DA在FEF内的作用介导的假设。在美国国家科学基金会的支持下，Noudoost博士及其同事将把电生理记录与局部神经活动的药理学操作配对，以揭示DA对注意力贡献的神经机制。一组实验将确定参与控制注意力和视觉信号的前额神经元的功能特征。使用改进的技术，将识别投射到视觉区域的前额叶神经元，表征其输出信号的内容，并确定该信号对视觉区域表征的影响。第二组实验将使用局部药理学操作来直接检查FEF DA是否足以产生由于注意力引起的感知和神经增强。总的来说，拟议的实验旨在确定神经元、神经调节剂以及前额叶和视觉皮层之间的相互作用，这些相互作用是根据任务需求灵活分配神经资源的基础；这样的理解将有助于深入了解这些过程的变化如何成为精神疾病中所见的注意力缺陷的基础，并可能提供新的诊断和治疗方法。长期以来，PFC多巴胺（DA）失衡一直被怀疑是精神疾病（如注意缺陷多动障碍）中注意力障碍的病因，多巴胺能药物在这些注意力障碍的治疗中发挥了核心作用。更好地了解这些过程背后的基本神经机制，最终将有助于开发诊断和治疗方法，改善受影响个体的福祉。该提案的一部分涉及与Neuralynx公司合作开发硬件，该公司位于实验室附近，是数据采集和信号处理行业中最重要的公司之一，从而促进工业界和学术界之间的伙伴关系，以开发新工具和实现新的实验技术。在美国国家科学基金会的支持下，PI将对三名女科学家进行尖端神经生理学研究技术和数据分析方面的培训。他们还将有机会在顶级学术期刊上发表他们的研究成果，并在国内和国际会议上向同事展示他们的研究成果。首席研究员及其同事亦会在大学公开展示研究结果，并向全体本科生广泛宣传，从而提高公众对科学研究的认识和欣赏。注意对学习至关重要，因此，更好地理解注意的机制也可以指导教育专业人员采取更有效的教学方法。

Attention is the means by which we focus on behaviorally relevant information, to select and enhance a subset of sensory information for further processing while ignoring the rest. Several decades of research have implicated the prefrontal cortex (PFC) in the control of attention. Previous studies have showed that the manipulation of DA-mediated activity within the frontal eye field (FEF) part of PFC enhances the strength of signals in visual areas, raising the hypothesis that prefrontal control of attention is mediated by the actions of DA within the FEF. With support from the National Science Foundation, Dr. Noudoost and colleagues will pair electrophysiological recordings with local pharmacological manipulation of neural activity to reveal the neural mechanisms underlying DA's contribution to attention. One set of experiments will determine the functional characteristics of prefrontal neurons involved in the control of attention and visual signals. Using an improved technique, the prefrontal neurons projecting to visual areas will be identified, the content of their outgoing signal will be characterized, and the impact of this signal on representations in visual areas will be determined. A second set of experiments will use local pharmacological manipulations to directly examine the sufficiency of FEF DA to produce the perceptual and neural enhancements due to attention. Collectively, the proposed experiments aim to determine the neurons, neuromodulators, and interactions between prefrontal and visual cortices that underlie the flexible allocation of neural resources according to task demands; such an understanding will provide insight into how changes in these processes underlie the attentional deficits seen in mental illnesses, potentially indicating new diagnostic and therapeutic approaches.An imbalance in PFC dopamine (DA) has long been a suspect in the etiology of attentional impairments in mental illnesses such as attention deficit hyperactivity disorder, and dopaminergic drugs have played a central role in the treatment of these attentional impairments. A better understanding of the basic neural mechanisms underlying these processes will ultimately help develop diagnostics and treatments improving the well-being of affected individuals. Part of this proposal involves hardware development in collaboration with Neuralynx Company, which is located near the lab and is one of the foremost companies in data acquisition and signal processing industry, thus fostering a partnership between industry and academia for developing new tools and enabling new experimental techniques. Through the support of the National Science Foundation, three female scientists will be trained by the PI in cutting-edge neurophysiological research techniques and data analysis. They will also have the opportunity to publish their research in top tier academic journals, and present their research to colleagues at national and international conferences. The PI and colleagues will also present the results of this research in public presentations at the university, and widely advertised to the entire undergraduate population, thereby raising public awareness of and appreciation for scientific research. Attention is critical for learning, and thus a better understanding of the mechanisms of attention can also guide educational professionals toward more effective pedagogic approaches.