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.

神经回路与行为表现之间的联系一直是神经科学的持久谜团。一个 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，从几分钟到几天到几天，以及许多空间 从局部神经元到整个大脑的鳞片。我们的一个重要缺少功能 对认知和行为的理解，这可能解释了一些明显的可变性，是缺乏洞察力 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（例如注意力或唤醒）至关重要。这种协调有 它们在现场电位水平上进行了广泛研究，但在单个神经元的种群中相对较少。 此外，由于一对大脑区域中神经元之间的协调可能与 远处的脑电路，嘲笑产生协调神经活动的基本神经环路 依次与行为的联系受到挑战。同时，针对的药物方法 在神经调节系统上，提供了一种强大的（即使粗糙），意味着影响行为和治疗疾病。 我们将从范围内研究的神经元配位，从测量的场电位和神经血管信号 头皮，皮质中的尖峰神经元种群，以深脑结构中的单个神经元 调节皮质活性。同时，我们还将衡量认知和感知任务的行为 作为学生，我们在以前的工作中显示 小时。我们的策略是确定皮质神经元的神经元协调如何表明内部认知 状态和神经调节输入，可以修改以改变认知和行为。我们将在 将人群中神经元之间的变异性与大脑内部状态联系起来的计算框架 并依靠行为。在我们的第一个具体目标中，我们将检验以下假设 头皮上的神经血管信号与前额叶皮层和行为中的神经元协调直接相关。 在第二个目标中，我们将检验以下假设：前额叶皮层中的神经元协调 唤醒的全身指标受到核基因座的去甲肾上腺素外排的影响。最后，在 第三目的，我们将通过微刺激轨迹来测试直接干预该电路中的假设 凝结可以改变皮质中的神经元协调，进而影响行为。总体结果 研究将是在皮层，神经调节驱动和协调活动之间建立直接联系 认知和行为。这将有助于开发涉及无数神经系统疾病的治疗方法 改变了唤醒状态或去甲肾上腺素驱动器的变化，并建立了一个理解的框架 神经元协调的大规模测量（例如头皮电位的振荡）和 神经元电路机制。