Distinct long-range inputs to prefrontal cortex coordinate visual decision making

项目总结/摘要 这项拟议研究的目标是了解前额叶中的知觉决策回路如何 大脑皮层（PFC）比较不同的感觉信息流来选择动作。大量的研究表明 前额叶皮层作为感知决策回路中的重要节点，在感觉神经系统中起着至关重要的作用。 代表性和行动选择。然而，前额叶皮层是如何利用感觉信号来产生选择信号的， 还不清楚我们实验室以前的工作表明，前扣带皮层（ACC），一个子区域， 在视觉引导的决策行为中起着重要的作用。此外，我们实验室的工作 其他人发现视觉皮层（VC）直接投射到ACC，并且ACC的半球 是紧密相连的我们最近的工作表明，这些输入将信息传递到大脑的每个半球。 前扣带回对侧和同侧半视野的变化。因此，这些途径提供了机会， 研究如何使用不同的感官信息流来产生知觉选择信号， 前额皮质我设计了一个两种选择的强制选择任务，要求比较 在视觉半视野中的会聚信息。头部固定的小鼠接受两种选择的强制选择训练 一项任务，要求他们比较两个半视野中的视觉线索，并报告目标线索的位置， 旋转球。我假设ACC整合了VC和ACC的输入，以指导这种情况下的行动选择。 行为我还提出，这种比较过程反映在ACC的感觉活动中， 代表性、证据和选择单元。为了评估这些假设，我将结合联合收割机这个复杂的 头部固定行为与区域和投影特异性光遗传学和体内多光子成像。在目标1中， 将使用区域光遗传学来确定VC和ACC对这种行为的贡献。我还将测试 假设来自VC和ACC轴突通过使用 投射特异性光遗传学在目标2中，我将使用双光子成像和种群解码来识别 行为小鼠前扣带回中的感觉表征、证据和选择细胞。然后，我将联合收割机 失活与双光子成像过程中的行为，以确定如何信息这两个途径 传达与感官表征、证据和选择细胞相互作用。这些实验将 确定ACC中视觉决策的不同输入的作用，并确定局部视觉感知 决策电路执行功能障碍在许多脑部疾病中的患病率以及 有针对性的治疗方法，以治疗他们敦促对大脑机制的基础研究，更高的认知 像决策这样的功能。通过确定远程和本地PFC电路对决策的贡献， 因此，这些研究可能会突出开发新治疗方法的关键目标。

Project Summary/Abstract The goal of the proposed research is to understand how perceptual decision-making circuits in the prefrontal cortex (PFC) compare distinct streams of sensory information to select actions. A large body of work identifies the PFC as an important node in perceptual decision-making circuits, with a critical role in sensory representation and action selection. However, how the PFC uses sensory signals to generation choice signals is unclear. Previous work from our laboratory has shown that the anterior cingulate cortex (ACC), a sub-region of PFC, plays an important role in visually guided decision-making behavior. Furthermore, work from our lab and others find that the visual cortex (VC) projects directly to the ACC, and that the hemispheres of the ACC are heavily interconnected. Our recent work shows that these inputs convey information to each hemisphere of the ACC about its contralateral and ipsilateral visual hemifield. Thus, these pathways provide an opportunity to examine how distinct streams of sensory information are used to generate perceptual choice signals in the prefrontal cortex. I have designed a two-alternative forced choice task that requires the comparison of convergent information across visual hemifields. Head-fixed mice are trained on a two-alternative forced choice task that requires them to compare visual cues in either hemifield and report the location of a target cue by rotating a ball. I hypothesize that the ACC integrates VC and ACC inputs to guide action selection in this behavior. I also propose that this comparison process is reflected in the activity of the ACC’s sensory representation, evidence, and choice cells. To evaluate these hypotheses, I will combine this sophisticated head-fixed behavior with areal and projection-specific optogenetics and in vivo multiphoton imaging. In Aim 1, I will determine the contributions of VC and ACC to this behavior using areal optogenetics. I will also test the hypothesis that axons from VC and ACC convey distinct information about either visual hemifield by using projection-specific optogenetics. In Aim 2, I will use two-photon imaging and population decoding to identify sensory representation, evidence, and choice cells in the ACC of behaving mice. Then, I will combine axonal inactivation with two-photon imaging during behavior to determine how the information these two pathways convey interacts with sensory representation, evidence, and choice cells. Together, these experiments will determine the role of distinct inputs to visual decision-making in the ACC and identify a local visual perceptual decision-making circuit. The prevalence of executive dysfunctions in numerous brain disorders and scarcity of targeted therapeutics to treat them urges basic research on the brain mechanisms underlying higher cognitive functions like decision-making. By identifying the contributions of long-range and local PFC circuits to decision- making, these studies may highlight critical targets for the development of novel treatments.