Midbrain circuits for perceptual decision-making

用于感知决策的中脑回路

• 批准号: 10216482
• 负责人: MARTHA E BICKFORD
• 金额: $ 378.46万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10216482
• 关键词: Address; Aging; Alzheimer' s Disease; Arbitration; Architecture; Area; Attention; Attention deficit hyperactivity disorder; Basal Ganglia; Behavior; Behavioral; Brain; Brain Stem; Brain region; Calcium; Cell Nucleus; Cells; Cerebral cortex; Computer Models; Coupled; Data; Decision Making; Decision Theory; Development; Discrimination; Disease; Dissection; Electrophysiology (science); Evaluation; Foundations; Future; Goals; Head; Human; Image; Impairment; In Vitro; Interneurons; Knowledge; Label; Link; Measures; Midbrain structure; Modeling; Monkeys; Motion; Motor; Mus; Nature; Neurodevelopmental Disorder; Neurons; Outcome; Parkinson Disease; Pattern; Peroxidases; Physiological; Physiology; Presynaptic Terminals; Primates; Process; Psychophysics; Pulvinar structure; Reporting; Research; Research Personnel; Role; Schizophrenia; Sensory; Series; Slice; Synapses; Techniques; Testing; Thalamic structure; Time; Translations; Tupaiidae; Viral; Visual; Visual Motion; area MT; autism spectrum disorder; behavior measurement; cell type; cognitive ability; cognitive function; daily functioning; design; experimental study; in vivo; mild cognitive impairment; neuronal circuitry; novel; optogenetics; relating to nervous system; superior colliculus Corpora quadrigemina; two-photon; visual processing

ABSTRACT Perceptual decision-making is a fundamental cognitive ability that is vital to healthy, daily functioning and is impaired in many diseases. Although many brain regions are known to be involved, there is no clear brain-wide model of how perceptual decisions are formed and executed and the underlying circuit mechanisms are still largely unknown. Here, a team of investigators propose a series of experiments that will use behavioral measures, imaging, physiology, circuit dissection, and computational modeling to study how the midbrain superior colliculus (SC) participates in visual decision-making. Specifically, this new team of investigators will probe the contribution of two SC neuronal cell types, wide field vertical (WFV) cells in the visuosensory layers and predorsal bundle (PDB) cells in the motor layers. These experiments will be done in mice and tree shrews, to reveal the underlying circuits and computational principles across species and to lay the foundation for future experiments designed to dissect decision-making circuits in primates. In Aim 1, the investigators will establish and perform psychophysical experiments to assess perceptual decision-making in both species. The behavioral data will be fitted with computational models to arbitrate between different theories of decision-making. In Aim 2, two photon calcium imaging and/or physiological recording will be performed in mice and tree shrews to determine the activity of WFV and PDB neurons during the psychophysical measures established in Aim 1. In addition, WFV and PDB neurons will be silenced optogenetically during the behavioral tasks to reveal their specific roles in decision-making. In Aim 3, the investigators will use intersectional monosynaptic viral tracing techniques, multiplexed peroxidase labeling for confocal and ultrastructural analysis of synaptic connections and and optogenetics-assisted brain slice recording to investigate the intrinsic and extrinsic circuits that link WFV and PDB cells. Together, these experiments will generate novel knowledge of the synapse to circuit mechanisms underlying perceptual decision-making, and provide technical and theoretical foundations for future mechanistic studies of cognitive function in higher mammalian species directly relevant to humans.

抽象的 知觉决策是一种基本的认知能力，对于健康、日常功能至关重要，并且 许多疾病都会受到损害。尽管已知许多大脑区域都参与其中，但尚无明确的全脑范围 感知决策如何形成和执行的模型以及底层电路机制仍然存在 很大程度上不为人知。在这里，一组研究人员提出了一系列实验，将使用行为 测量、成像、生理学、电路解剖和计算模型来研究中脑如何 上丘（SC）参与视觉决策。具体来说，这个新的调查小组将 探测两种 SC 神经元细胞类型的贡献，即视觉感觉层中的宽视野垂直 (WFV) 细胞 和运动层中的前背束（PDB）细胞。这些实验将在老鼠和树鼩身上进行， 揭示跨物种的底层电路和计算原理，并为未来奠定基础 旨在剖析灵长类动物决策回路的实验。在目标 1 中，研究人员将确定 并进行心理物理学实验来评估这两个物种的感知决策。行为方面 数据将与计算模型相匹配，以在不同的决策理论之间进行仲裁。在目标 2 中， 将在小鼠和树鼩中进行两个光子钙成像和/或生理记录，以 确定目标 1 中建立的心理物理测量期间 WFV 和 PDB 神经元的活动。 此外，在行为任务期间，WFV 和 PDB 神经元将被光遗传学沉默，以揭示它们的作用 决策中的具体角色。在目标 3 中，研究人员将使用交叉单突触病毒追踪 技术，用于突触连接的共聚焦和超微结构分析的多重过氧化物酶标记和 和光遗传学辅助脑切片记录，以研究连接 WFV 的内在和外在回路 和 PDB 细胞。这些实验将共同产生关于突触到电路机制的新知识 底层感知决策，为未来机械论提供技术和理论基础 与人类直接相关的高等哺乳动物物种的认知功能研究。