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

注意力是我们专注于与行为相关的信息，以选择和增强感官信息的子集进行进一步处理，而忽略其余信息的手段。几十年的研究表明，前额叶皮质(PFC)参与了注意力的控制。以往的研究表明，在PFC的额叶眼区(FEF)内操纵DA介导的活动增强了视觉区域中的信号强度，从而提出了注意的前额叶控制是由FEF内的DA调节的假说。在国家科学基金会的支持下，Noudoost博士和他的同事们将把电生理记录与神经活动的局部药物操作配对，以揭示DA对注意力贡献的神经机制。其中一组实验将确定参与控制注意力和视觉信号的前额叶神经元的功能特征。使用一种改进的技术，投射到视觉区域的前额神经元将被识别，其输出信号的内容将被表征，并且该信号对视觉区域表征的影响将被确定。第二组实验将使用局部药理学操作来直接检查FEF DA的充分性，以产生由于注意而产生的知觉和神经增强。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质之间的相互作用，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是如何导致精神疾病中出现的注意力缺陷的，从而潜在地指示新的诊断和治疗方法。长期以来，PFC多巴胺(DA)的失衡一直是注意力缺陷(如注意缺陷多动障碍)的病因学中的一个可疑因素，而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，改善受影响个人的福祉。该提案的一部分涉及与Neuralynx公司合作进行硬件开发，Neuralynx公司位于实验室附近，是数据采集和信号处理行业的领先公司之一，从而促进了业界和学术界之间在开发新工具和支持新实验技术方面的合作伙伴关系。通过国家科学基金的支持，三名女科学家将接受PI在尖端神经生理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。PI和他的同事还将在大学的公开演讲中展示这项研究的结果，并向所有本科生广泛宣传，从而提高公众对科学研究的认识和欣赏。注意力对学习至关重要，因此，更好地理解注意力的机制也可以引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.