Multimodal characterization of prefrontal and premotor circuits underlying perceptual decision making in therhesus monkey

恒河猴知觉决策的前额叶和运动前回路的多模态特征

• 批准号: 10441553
• 负责人: Chandramouli Chandrasekaran
• 金额: $ 65.58万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10441553
• 关键词: Action Potentials; Address; Anatomy; Animals; Area; Automobile Driving; Behavioral; Biophysics; Brain; Brain Injuries; Cells; Clinical Research; Computer Models; Cues; Data; Decision Making; Development; Discrimination; Dorsal; Electrodes; Electrophysiology (science); Etiology; Feedback; Fiber; Frequencies; Future; Goals; Impairment; In Vitro; Lateral; Lead; Lesion; Life; Light; Membrane; Mental disorders; Methods; Modeling; Monkeys; Morphology; Movement Disorders; Nature; Neurodegenerative Disorders; Neurons; Opsin; Optical Methods; Optics; Pathway interactions; Pattern; Physiological; Play; Prefrontal Cortex; Process; Property; Recovery; Recovery of Function; Research; Resolution; Role; Sensory; Short-Term Memory; Signal Transduction; Site; Slice; Source; Structure; Synapses; Techniques; Testing; Therapeutic; Tracer; Training; Vision; Work; anatomical tracing; base; biocytin; biophysical properties; brain machine interface; cell type; clinically relevant; density; executive function; experimental study; in vivo; insight; morphometry; multimodality; neural patterning; neurophysiology; next generation; novel; patch clamp; relating to nervous system; response; sensory input; sensory stimulus; stroke patient

Abstract: The objective of the proposed research is to understand the diverse lamina-specific neurons, and connections between the dorsolateral prefrontal cortex (DLPFC) and the rostral aspect of the dorsal premotor cortex (PMdr) during decision-making. Decision-making refers to our ability to choose and perform appropriate actions based on sensory cues and context to achieve behavioral goals. Pressing the brakes to stop the car in response to a red light or choosing what dress to wear are common decisions that we make in our everyday life. Disrupted activity in brain areas such as the DLPFC and PMdr contribute to the impairments in decision-making observed in mental illness. Our past work and other research has provided some insight into the involvement of DLPFC and PMdr in decision-making and that these areas are strongly interconnected. However, we currently do not understand 1) the relationship between biophysical properties and morphological structure, and in vivo decision-related activity of neurons in different layers of these brain areas, and 2) whether the connections between DLPFC and PMdr are feedforward, feedback or lateral (both feedforward and feedback). We address these open questions by using a multimodal approach that combines in vivo neurophysiology in DLPFC and PMdr of behaving monkeys, decoding and granger causality analysis, optical stimulation of DLPFC inputs to PMdr, tract tracing experiments and in vitro single neuron electrophysiology and morphometry in slices from the same subjects. Our first aim uses laminar multi-contact electrodes to investigate neuronal responses across layers of PMdr, and DLPFC while monkeys perform a novel decision-making task that separates perceptual decisions from action selection. We will investigate if in vivo differences are related to differences in biophysical and morphological properties of these neurons with in vitro whole-cell patch-clamp recordings of lamina-specific neurons in PMdr slices. In Aim 2, we examine the granger causality between the local field potentials recorded simultaneously in DLPFC and PMdr to understand whether DLPFC sends a feedforward driving input or a modulating feedback input. We combine these in vivo experiments with anatomical tracing experiments in DLPFC to understand the bidirectional laminar pattern of DLPFC and PMdr connections. In Aim 3, we will inject an opsin in DLPFC and stimulate the anterograde fibers in PMdr in vivo to causally investigate whether the pattern of activity induced in PMdr by stimulation of DLPFC is consistent with feedforward, feedback, or lateral connections. To obtain a more detailed understanding of the pattern of inputs from DLPFC to PMdr, we will investigate in vitro synaptic responses of these PMdr neurons in layers 3 and 5 to optical stimulation of afferent DLPFC fibers and localize the morphological compartments of PMdr neurons to which DLPFC afferent fibers provide inputs. Impact: This project will elucidate the in vivo and in vitro laminar dynamics within and interactions between two critical, clinically relevant brain areas. Such data is a prerequisite for future development of circuit- level therapeutics for mental illness and brain machine interfaces for recovery following brain injury.

翻译后摘要：拟议的研究的目的是了解不同的板层特异性神经元， 背外侧前额叶皮层（DLPFC）和背侧前运动区吻侧之间的联系 Pmdr（英语：Pmdr）在决策过程中。决策是指我们选择和执行适当的能力 基于感官线索和背景的行动，以实现行为目标。踩刹车使汽车停下来 对红灯的反应或选择穿什么衣服是我们日常生活中常见的决定。 大脑区域（如DLPFC和PMdr）的活动中断会导致决策障碍 在精神疾病中观察。我们过去的工作和其他研究提供了一些见解， DLPFC和PMDR在决策中的作用，这些领域密切相关。然而，我们目前 不了解1）生物物理特性和形态结构之间的关系，以及体内 这些大脑区域不同层中神经元的决策相关活动，以及2）连接是否 DLPFC和PMdr之间的关系是前馈、反馈或横向（前馈和反馈两者）。我们解决 这些开放的问题，通过使用多模式的方法，结合体内神经生理学在DLPFC和 行为猴子的PMDR，解码和格兰杰因果关系分析，DLPFC输入的光学刺激， PMDR、束示踪实验和体外单神经元电生理学和形态计量学研究 同样的主题。我们的第一个目标是使用层状多接触电极来研究神经元的反应， 当猴子执行一项新的决策任务时， 行动选择的决定。我们将研究体内差异是否与生物物理学差异有关。 这些神经元的形态学特性与体外全细胞膜片钳记录的板层特异性 PMDR切片中的神经元。在目标2中，我们研究了记录的局部场电位之间的格兰杰因果关系 同时在DLPFC和PMdr中，以了解DLPFC是否发送前馈驱动输入或 调制反馈输入。我们将联合收割机这些体内实验与解剖学示踪实验相结合， DLPFC以了解DLPFC和PMdr连接的双向层状模式。在目标3中，我们将注入 在DLPFC中的视蛋白，并刺激体内PMdr中的顺行纤维，以因果地研究DLPFC中的 通过刺激DLPFC在PMdr中诱导的活动模式与前馈、反馈或横向一致。 连接.为了更详细地了解从DLPFC到PMdr的输入模式，我们将 研究这些第3和第5层PMdr神经元对传入纤维光刺激的体外突触反应 DLPFC纤维和定位PMdr神经元的形态室，DLPFC传入纤维 提供投入。影响：本项目将阐明体内和体外层流动力学和相互作用 两个重要的临床相关脑区之间的联系这些数据是未来电路发展的先决条件- 水平治疗精神疾病和脑机接口恢复脑损伤后。