Rigourous behavioral paradigms for visuospatial attention

项目总结 注意力是动物选择和优先处理最重要的或最高的东西的非凡能力 优先级“，在复杂环境中指导行为的信息。这种动态能力对于一系列 认知功能和适应行为，以及它的功能障碍在各种精神疾病中被发现，包括 多动症、自闭症和精神分裂症。然而，人们对大脑的回路机制几乎一无所知 随时执行最高优先级刺激的选择。减缓进展的一个关键因素 几乎只有灵长类动物被用来研究注意力：缺乏多样化的遗传工具 在灵长类动物中的使用排除了对细胞类型特定贡献和神经的系统剖析 用于注意力控制的大脑皮层和皮质下回路的计算。另一个是严格的行为 研究注意力的范例目前在任何其他(遗传上容易驯服的)哺乳动物物种中都不存在。至 为了弥补这一差距，我们提出了一种创新的替代方法：开发参数化的、类似灵长类动物的行为 小鼠视觉空间注意的范例，以便遗传技术提供的全部力量 可以利用小鼠模型来剖析注意力控制的神经回路。在这里，我们将 在行为自由的小鼠中开发基于触摸屏的任务，以研究注意力。具体来说，在目标1中，我们将 为研究空间注意的外源性(自下而上)控制，发展了三个参数任务，即 波斯纳辨别任务、侧翼任务和波斯纳提示的选择任务。在目标2中，我们将开发两个 研究空间注意内源性(自上而下)控制的参数任务，即空间期望 任务和自上而下的空间线索选择任务。此外，在Aim 3中，我们将使用头部和眼睛跟踪器来 开发一种闭环刺激呈现系统，该系统实时调整刺激位置 自由行为的鼠标的凝视方向。这将允许刺激在视网膜上的一致呈现 在上述任务中的试验，未来试验的要求为功能签名以及因果作用 空间注意控制中的神经回路。初步的行为数据支持这三种方法的可行性 建议的目标。这是第一次在遗传学上对空间注意的严格范式的发展 易驯化的哺乳动物模型将为未来解开神经机制的工作建立一个强大的新平台 注意力控制，以及注意力被干扰的神经信息处理通路 功能障碍。

PROJECT SUMMARY Attention is the remarkable ability of animals to select and preferentially process the most important, or “highest priority”, information in complex environments to guide behavior. This dynamic ability is essential for a range of cognitive functions and adaptive behavior, and its dysfunction is found in diverse psychiatric illnesses including ADHD, autism and schizophrenia. Yet, almost nothing is known about the circuit mechanisms by which the brain implements the selection of the highest priority stimulus at any instant. One key factor that has slowed progress has been the nearly exclusive use of primates for the study of attention: the absence of diverse genetic tools for use in primates has precluded the systematic dissection of cell-type specific contributions and neural computations in cortical and subcortical circuits in service of attention control. Another is that rigorous behavioral paradigms to study attention do not currently exist in any other (genetically tractable) mammalian species. To bridge this gap, we propose an innovate alternate approach: to develop parameterized, primate-like behavioral paradigms for visuospatial attention in the mouse so that the full power of genetic techniques offered by the mouse model can be brought to bear to dissect the neural circuitry underlying attention control. Here, we will develop touchscreen-based tasks in freely behaving mice for studying attention. Specifically, in Aim 1, we will develop three parameterized tasks for studying exogenous (bottom-up) control of spatial attention, namely, a Posner discrimination task, a flanker task, and a Posner-cued selection task. In Aim 2, we will develop two parameterized tasks for studying endogenous (top-down) control of spatial attention, namely, a spatial expectation task and a top-down spatially-cued selection task. Additionally, in Aim 3, we will use head and eye-trackers to develop a closed-loop stimulus presentation system that adjusts, in real time, stimulus locations with respect to the gaze direction of the freely behaving mouse. This will permit consistent retinotopic presentation of stimuli across trials in the above tasks, a requirement for future experiments into the functional signatures as well as causal roles of neural circuits in spatial attention control. Preliminary behavioral data support the feasibility of all three proposed aims. This development, for the first time, of rigorous paradigms for spatial attention in a genetically tractable mammalian model will establish a powerful new platform for future work unraveling neural mechanisms of attention control, as well as of neural information processing pathways that are disrupted in attentional dysfunction.