Midbrain circuits for perceptual decision-making

用于感知决策的中脑回路

基本信息

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
项目类别：
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&apos 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

项目摘要

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。