Midbrain Circuits for Perceptual Decision-Making

摘要 感知决策是一种基本的认知能力，对健康的日常运作至关重要， 在许多疾病中受损。尽管已知许多大脑区域都参与其中，但还没有明确的全脑范围的 感知决策如何形成和执行的模型，以及底层的电路机制仍然是 大部分未知。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，电路解剖和计算建模，以研究中脑如何 上级丘参与视觉决策。具体来说，这支新的调查团队将 探讨SC两种神经元细胞类型、视感觉层中的宽视野垂直（WFV）细胞的贡献 和运动层中的背前束（PDB）细胞。这些实验将在老鼠和树鼩身上进行， 揭示跨物种的潜在电路和计算原理，并为未来的研究奠定基础。 旨在剖析灵长类动物决策回路的实验。在目标1中，研究人员将建立 并进行心理物理实验，以评估两个物种的感知决策。行为 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双光子钙成像和/或生理记录， 在目标1中建立的心理物理测量期间确定WFV和PDB神经元的活性。在 此外，WFV和PDB神经元将在行为任务期间被光遗传学沉默，以揭示它们的功能。 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， 和光遗传学辅助的脑切片记录来研究连接WFV的内在和外在回路 和PDB细胞。总之，这些实验将产生新的知识的突触电路机制 潜在的感知决策，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.