Understanding the prefrontal mechanisms involved in the enhancement and maintenance of visual signals

工作记忆和注意力，都是执行功能的关键组成部分，也是灵活的，目标- 驱动行为，在多种认知障碍中共同受损，包括帕金森病， 精神分裂症和注意力缺陷多动障碍。几十年的研究表明 前额叶皮层（PFC）控制注意力和工作记忆。尽管最近有证据表明 表明视觉信息的表征是由工作记忆的内容调节的， 对这种调制的神经机制知之甚少。该项目旨在实现 我们使用非常直接的方法对这些机制的理解取得了根本性的进展： 识别参与与视觉皮层相互连接的PFC神经元，测量动态 PFC输入强度的变化，以及神经元活动的局部药理学操作。的 神经科学家描述产生认知功能的神经机制的能力， 由于难以将解剖学和电生理学特征结合起来， 神经元目标1将结合联合收割机在线尖峰波形鉴别，阵列记录， 和定制硬件，以生产一个高效的，半自动化的系统， 大脑区域之间的连接。该系统将与数据采集部门合作开发 硬件公司Neuralynx，并为神经生物学家提供了一个高通量的工具来研究 大脑网络的连通性，显著增强了我们解开特定功能回路的能力。 该系统将用于研究工作时前额叶皮层与视皮层之间的信息交流 记忆初步数据表明，工作记忆活动是PFC神经元的关键特征 投射到视觉皮层接下来，视觉反应如何根据工作记忆的内容而变化 将被衡量。最后，多巴胺介导的前额叶活动是否足以驱动这些 视觉处理的变化将使用局部药物输注直接测试。目标2审查了 前额叶皮层空间活动对视觉皮层客体记忆维持的影响， 以及内存性能。多巴胺能前额叶活动对神经元和 将因果地测试对象工作记忆的行为相关性。这些目标将共同提供 PFC和视觉皮层之间的相互作用如何依赖于 工作记忆的内容;这样的理解将提供洞察的相互依存关系， 注意力和工作记忆，以及工作记忆缺陷如何与 视觉信息的处理，这在精神疾病中经常被观察到。

Working memory and attention, both critical components of executive function and flexible, goal- driven behavior, are jointly impaired in multiple cognitive disorders, including Parkinson's disease, schizophrenia, and attention deficit hyperactivity disorder. Several decades of research have implicated the prefrontal cortex (PFC) in the control of attention and working memory. In spite of recent evidence indicating that the representation of visual information is modulated by the contents of working memory, little is known about the neural mechanisms underlying this modulation. This project aims to achieve a fundamental advance in our understanding of these mechanisms using very direct approaches: identifying PFC neurons involved in reciprocal connections with visual cortex, measuring dynamic changes in the strength of PFC inputs, and local pharmacological manipulations of neuronal activity. The ability of neuroscientists to describe the neural mechanisms giving rise to cognitive functions has long been hampered by the difficulty of combining anatomical and electrophysiological characterization of neurons. Aim 1 will combine recent advances in online spike waveform discrimination, array recording, and custom hardware to produce a highly efficient, semi-automated system for the screening of connectivity between brain areas. This system will be developed in collaboration with data acquisition hardware company Neuralynx, and provide neurobiologists a high-throughput tool to study the connectivity of brain networks, significantly enhancing our ability to untangle functionally specific circuits. This system will be used to examine communication between PFC and visual cortex during working memory. Preliminary data indicate that working memory activity is the key characteristic of PFC neurons projecting to visual cortex. Next, how visual responses change based on the contents of working memory will be measured. Lastly, whether dopamine-mediated prefrontal activity is sufficient to drive these changes in visual processing will be directly tested using localized drug infusions. Aim 2 examines the impact of spatial activity in prefrontal cortex on the maintenance of an object memory in visual cortex, and on memory performance. The contribution of dopaminergic prefrontal activity to the neural and behavioral correlates of object working memory will be causally tested. Together, these aims will provide a detailed mechanistic account of how the interactions between PFC and visual cortex depend upon the contents of working memory; such an understanding will provide insight into the interdependence of attention and working memory, and how working memory deficits are associated with impairments in the processing of visual information, as is often observed in mental illnesses.