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Slow time scale fluctuations in neurons and behavior

神经元和行为的缓慢时间尺度波动

基本信息

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
项目类别：
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

项目摘要

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领域的一个谜。一个