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

前额皮质的独特远程输入协调视觉决策

• 批准号: 10461074
• 负责人: Karen Guadalupe Cruz
• 金额: $ 3.03万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-01-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10461074
• 关键词: Anatomy; Anterior; Attention Deficit Disorder; Axon; Basic Science; Behavior; Behavioral; Brain; Brain Diseases; Calcium; Cells; Clinical; Complex; Contralateral; Cues; Decision Making; Development; Disease; Dissection; Executive Dysfunction; Generations; Goals; Head; Image; Impairment; Ipsilateral; Knowledge; Laboratories; Learning; Life; Location; Medial; Mediating; Mental Depression; Midbrain structure; Motor; Mus; Neurons; Output; Pathway interactions; Play; Population; Prefrontal Cortex; Prevalence; Primates; Process; Psychometrics; Psychophysics; Reporting; Research; Role; Schizophrenia; Sensory; Signal Transduction; Stimulus; Stream; Techniques; Testing; Trackball Device Component; Training; Visual; Visual Cortex; Work; cell cortex; cell type; cingulate cortex; cognitive function; cognitive process; computerized tools; design; executive function; experimental study; frontal eye fields; frontal lobe; in vivo; information model; information processing; luminance; microstimulation; multiphoton imaging; multiphoton microscopy; neural circuit; neuromechanism; neurophysiology; neuropsychiatric disorder; nonhuman primate; novel; optogenetics; relating to nervous system; sensory cortex; superior colliculus Corpora quadrigemina; targeted treatment; tool; two-photon; visual information; visual motor; visual stimulus

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.

项目摘要/摘要 这项拟议的研究的目标是了解知觉决策是如何在前额叶中循环的。 大脑皮层(PFC)比较不同的感觉信息流来选择动作。大量的工作确定了 PFC作为知觉决策回路中的一个重要节点，在感觉中起着至关重要的作用 表示和动作选择。然而，PFC如何使用感觉信号来产生选择信号 目前还不清楚。我们实验室以前的工作表明，前扣带回皮质(ACC)是一个亚区 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 另一些人发现，视觉皮质(VC)直接投射到ACC，而ACC的半球 是高度相互关联的。我们最近的研究表明，这些输入将信息传递到大脑的每个半球 ACC的对侧和同侧视野。因此，这些途径提供了一个机会 研究不同的感觉信息流是如何用来在 前额叶皮质。我设计了一个两种选择的强迫选择任务，它需要比较 跨视觉半视野的信息汇聚。头部固定的小鼠接受了两种选择的强迫选择训练 一项任务，要求他们比较两个半场中的视觉线索，并通过以下方式报告目标线索的位置 旋转一个球。我假设ACC集成了VC和ACC输入来指导在这方面的行动选择 行为。我还认为，这种比较过程反映在ACC的感官活动中 代表、证据和选择单元格。为了评估这些假设，我将结合这个复杂的 头部固定行为与区域和投影特定的光遗传学和活体多光子成像。在目标1中，我 将利用区域光遗传学来确定VC和ACC对这种行为的贡献。我还会测试一下 假设来自VC和ACC的轴突通过使用 特定于投影的光遗传学。在目标2中，我将使用双光子成像和布居解码来识别 行为小鼠ACC中的感觉表征、证据和选择细胞。然后，我会结合轴突 用双光子失活过程中的行为成像来确定这两条通路是如何传递信息的 传达与感觉表征、证据和选择细胞相互作用。总而言之，这些实验将 在ACC中确定不同输入对视觉决策的作用，并识别局部视觉知觉 决策巡回。执行功能障碍在许多大脑疾病中的流行率和缺乏 治疗这些疾病的靶向疗法促使人们对高认知能力背后的大脑机制进行基础研究 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。

项目成果

Distinct prefrontal top-down circuits differentially modulate sensorimotor behavior.

• DOI: 10.1038/s41467-020-19772-z
• 发表时间: 2020-11-26
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Huda R;Sipe GO;Breton-Provencher V;Cruz KG;Pho GN;Adam E;Gunter LM;Sullins A;Wickersham IR;Sur M
• 通讯作者: Sur M