Midbrain circuits for perceptual decision-making

摘要 知觉决策是一种基本的认知能力，对健康的日常运作至关重要，而且 在许多疾病中受损的。尽管已知有许多脑区参与，但没有明确的全脑范围。 感知决策如何形成和执行的模型，以及潜在的电路机制仍然是 很大程度上是未知的。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、电路解剖和计算建模来研究中脑是如何 上丘(SC)参与视觉决策。具体地说，这支新的调查团队将 两种SC神经元类型广野垂直(WFV)细胞在视感觉层中的作用 运动层的背前束细胞。这些实验将在老鼠和树鼠身上进行， 揭示跨物种的潜在电路和计算原理，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，调查人员将确定 并进行心理物理实验，以评估这两个物种的知觉决策。行为上的 数据将与计算模型相适应，以在不同的决策理论之间进行仲裁。在目标2中， 将在小鼠和树鼠身上进行双光子钙成像和/或生理记录，以 确定WFV和PDB神经元在目标1中建立的心理物理测量期间的活动 此外，WFV和PDB神经元将在行为任务期间被光遗传沉默，以揭示它们的 在决策中的具体作用。在目标3中，研究人员将使用交叉单突触病毒跟踪 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技术和 以及光遗传学辅助的脑片记录，以研究连接WFV的内在和外在电路 和PDB细胞。总之，这些实验将产生有关突触到电路机制的新知识 为感知决策提供基础，并为未来的机械化提供技术和理论基础 研究与人类直接相关的高等哺乳动物物种的认知功能。

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.