Slow time scale fluctuations in neurons and behavior

神经元和行为的缓慢时间尺度波动

• 批准号: 10521614
• 负责人: MATTHEW A SMITH
• 金额: $ 44.97万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10521614
• 关键词: Affect; Area; Arousal; Attention; Behavior; Behavioral; Bilateral; Blood; Blood Vessels; Brain; Brain Diseases; Brain region; Cerebrum; Clinical; Cognition; Cognitive; Communication impairment; Diagnosis; Diffuse; Dimensions; Disease; Distant; Electroencephalography; Electrophysiology (science); Exhibits; Functional Magnetic Resonance Imaging; Hour; Individual; Intervention; Lead; Link; Magnetism; Measurable; Measurement; Measures; Neuromodulator; Neurons; Neurosciences; Norepinephrine; Outcomes Research; Pattern; Perception; Performance; Pharmacological Treatment; Pharmacology; Play; Population; Prefrontal Cortex; Pupil; Research; Role; Scalp structure; Shapes; Signal Transduction; Structure; System; Techniques; Testing; Time; Utah; Waxes; Work; base; behavior influence; cognitive ability; cognitive process; computer framework; design; electrical microstimulation; experimental study; high dimensionality; indexing; insight; locus ceruleus structure; nervous system disorder; neural circuit; neuronal circuitry; neuroregulation; neurovascular; nonhuman primate; relating to nervous system; temporal measurement

The link between neural circuits and behavioral performance has been an enduring mystery in neuroscience. A fundamental observation of both neurons and behavior has been that they both exhibit variability. This variability can manifest on a variety of time scales, from minutes to hours to days, and across many spatial scales, from local populations of neurons to the whole brain. One important missing feature in our understanding of cognition and behavior, that may explain some of the apparent variability, is a lack of insight into the brain’s internal cognitive state while performing any task. The coordination among neurons across the brain is critical to achieving any internal cognitive state, such as attention or arousal. This coordination has been extensively studied at the level of field potentials, but relatively rarely in populations of single neurons. Furthermore, because the coordination among neurons in a pair of brain areas may relate to the action of distant brain circuits, teasing apart the fundamental neural circuits that give rise to coordinated neural activity, and the link in turn to behavior, has been challenging. At the same time, pharmacological approaches targeted at neuromodulatory systems have proved a powerful, if coarse, means to influence behavior and treat disease. We will study neural coordination across scales, from field potentials and neurovascular signals measured at the scalp, to populations of spiking neurons in cortex, to individual neurons in a deep brain structure that modulates cortical activity. Simultaneously, we will measure behavior on cognitive and perceptual tasks as well as the pupil, which we have shown in previous work exhibit slow fluctuations on the time scale of minutes to hours. Our strategy is to identify how neuronal coordination of cortical neurons is indicative of internal cognitive state and neuromodulatory input, and can be modified to alter cognition and behavior. We will do this in a computational framework that links the variability among neurons in a population to internal states of the brain and in turn to behavior. In our first specific aim, we will test the hypothesis that field potentials and neurovascular signals at the scalp are directly linked to neuronal coordination in prefrontal cortex and behavior. In the second aim, we will test the hypothesis that neuronal coordination in prefrontal cortex as well as systemic indicators of arousal are influenced by norepinephrine efflux from the locus coeruleus. Finally, in the third aim, we will test the hypothesis that direct intervention in this circuit by microstimulating the locus coeruleus can alter neuronal coordination in cortex and in turn influence behavior. The overall result of this study will be to establish a direct link between coordinated activity in the cortex, neuromodulatory drive, and cognition and behavior. This will aid in developing treatments for myriad neurological disorders that involve altered states of arousal or changes in norepinephrine drive, and establish a framework for understanding the link between large-scale measures of neuronal coordination (like oscillations in field potentials at the scalp) and neuronal circuit mechanisms.

神经回路和行为表现之间的联系一直是神经科学中一个持久的谜团。一 对神经元和行为的基本观察是它们都表现出可变性。这 可变性可以在各种时间尺度上表现出来，从几分钟到几小时到几天， 从局部神经元群体到整个大脑。我们的一个重要的缺失特征 对认知和行为的理解，可以解释一些明显的变化，是缺乏洞察力 在执行任何任务时进入大脑的内部认知状态。神经元之间的协调 大脑对于实现任何内部认知状态（如注意力或唤醒）至关重要。这种协调 在场电位水平上进行了广泛的研究，但在单个神经元群体中相对较少。 此外，由于一对脑区中神经元之间的协调可能与 遥远的大脑回路，把引起协调神经活动的基本神经回路分开， 以及与行为之间的联系，一直是一个挑战。与此同时，药理学方法针对 研究神经调节系统已被证明是影响行为和治疗疾病的一种有力的手段，尽管是粗糙的手段。 我们将研究跨尺度的神经协调，从场电位和神经血管信号测量， 头皮，到皮层中的尖峰神经元群体，到深层大脑结构中的单个神经元， 调节皮层活动同时，我们也将测量认知和感知任务的行为 作为瞳孔，我们在以前的工作中已经表明，在几分钟的时间尺度上表现出缓慢的波动， 小时我们的策略是确定皮层神经元的神经元协调是如何指示内部认知的 状态和神经调节输入，并且可以被修改以改变认知和行为。我们将在一个 一种计算框架，将群体中神经元之间的变异性与大脑的内部状态联系起来 进而影响行为。在我们的第一个具体目标中，我们将测试场电位和 头皮上的神经血管信号与前额皮质的神经元协调和行为直接相关。 在第二个目标中，我们将检验前额叶皮层神经元协调以及 觉醒的系统性指标受到来自蓝斑的去甲肾上腺素流出的影响。最后在 第三个目标，我们将测试的假设，直接干预在这个电路通过微刺激的轨迹 蓝斑可以改变皮层神经元的协调性，进而影响行为。这一切的总体结果 这项研究将建立大脑皮层协调活动、神经调节驱动和 认知和行为。这将有助于开发治疗无数神经系统疾病的方法， 改变唤醒状态或去甲肾上腺素驱动的变化，并建立一个框架，了解 神经元协调的大规模测量（如头皮场电位的振荡）与 神经回路机制