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: 10693284
• 负责人: MATTHEW A SMITH
• 金额: $ 45.07万
• 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/10693284
• 关键词: Affect; Area; Arousal; Attention; Behavior; Behavior Control; 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; Hour; Individual; Intervention; Link; Magnetism; Measurable; Measurement; Measures; Neuromodulator; Neurons; Neurosciences; Norepinephrine; Outcomes Research; Pattern; Perception; Performance; Pharmacological Treatment; Play; Population; Prefrontal Cortex; Pupil; Research; Role; Scalp structure; Shapes; Signal Transduction; Structure; System; Techniques; Testing; Time; Utah; Waxes; Work; behavior influence; cognitive ability; cognitive process; computer framework; design; electrical microstimulation; experimental study; functional magnetic resonance imaging/electroencephalography; high dimensionality; indexing; insight; locus ceruleus structure; nervous system disorder; neural; neural circuit; neuronal circuitry; neuroregulation; neurovascular; nonhuman primate; pharmacologic; 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。 对神经元和行为的基本观察是它们都表现出可变性。 变异性可​​以在多种时间尺度上表现出来，从几分钟到几小时到几天，并且跨越许多空间 从局部神经元群到整个大脑的一个重要缺失特征。 对认知和行为的理解可能会解释一些明显的变异性，但缺乏洞察力 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（例如注意力或唤醒）至关重要。 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的研究相对较少。 此外，由于一对大脑区域中神经元之间的协调可能与 遥远的大脑回路，梳理引起协调神经活动的基本神经回路， 以及与行为的联系一直具有挑战性，同时，药理学方法也具有针对性。 神经调节系统的研究已被证明是一种影响行为和治疗疾病的强大手段，尽管粗略。 我们将通过测量的场电位和神经血管信号来研究跨尺度的神经协调 头皮、皮层中的尖峰神经元群、大脑深层结构中的单个神经元 同时，我们还将测量认知和感知任务的行为。 正如我们在之前的工作中所展示的瞳孔在分钟到分钟的时间尺度上表现出缓慢的波动 我们的策略是确定皮质神经元的神经协调如何指示内部认知。 状态和神经调节输入，并且可以进行修改以改变认知和行为。 将群体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 反过来，在我们的第一个具体目标中，我们将检验场势和场势的假设。 头皮的神经血管信号与前额皮质和行为的神经协调直接相关。 在第二个目标中，我们将检验以下假设：前额叶皮层的神经协调以及 唤醒的全身指标受到蓝斑去甲肾上腺素流出的影响。 第三个目标，我们将测试通过微刺激基因座直接干预该回路的假设 蓝藻可以改变皮层的神经协调，进而影响行为的总体结果。 研究将建立皮层协调活动、神经调节驱动和神经调节之间的直接联系 这将有助于开发涉及多种神经系统疾病的治疗方法。 改变唤醒状态或去甲肾上腺素驱动力的变化，并建立一个框架来理解 神经协调的大规模测量（如头皮场电位的振荡）和 神经回路机制。