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The neurobiology of global state transitions

全局状态转换的神经生物学

基本信息

批准号：
10326370
负责人：
Brenna Shortal
金额：
$ 2.58万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-01 至 2022-02-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10326370
关键词：
3-Dimensional Acute Address American Anesthesia procedures Anesthetics Animals Area Automobile Driving Behavioral Biophysical Process Brain Characteristics Chronic Communication Conscious Data Detection Dimensions Electrodes Electroencephalography Environment Exhibits Exposure to Frequencies General Anesthesia Generations Goals Grant Human Implant Individual Isoflurane Knowledge Measures Methodology Methods Modeling Neurobiology Neurons Operative Surgical Procedures Patients Pattern Pennsylvania Persons Population Publishing Rattus Reproducibility Research Personnel Resolution Risk Rodent Sampling Scientist Silicon Sleep Sleep Architecture Sleep Deprivation Sleep Disorders Sleep Stages Sleeplessness Slow-Wave Sleep Testing Time Tissues Unconscious State Universities Wakefulness awake base career circadian experimental study falls fascinate medical schools neurophysiology new technology novel vehicular accident

项目摘要

Project Summary Sleep has long fascinated scientists and philosophers alike. To date, the sleep field has made enormous strides towards explaining how the activity patterns recorded during sleep stages are generated. However, the transitions between wakefulness and sleep and between the stages of sleep are understudied. Sleep and wake promoting neuronal populations exhibit self-excitation and mutual inhibition12–16 which is thought to give rise to a winner-take-all strategy.17,18 This has typically been assumed to mean states of wake and sleep cannot coexist in the brain. However, from several specialized classes of species that engage in uni- hemispheric sleep, we know it is possible for part of the brain to fall asleep while another remains awake.18,19,21,22 During local sleep episodes recorded in rats, spatially restricted pockets of cortical tissue entered a slow wave rhythm of activity during behavioral wakefulness.23 Our lab and others have demonstrated that activity in the cortex undergoes state transitions during general anesthesia as well.27,28 What remains unknown is whether local state transitions are a general mechanism for transitions between consciousness and unconsciousness or if they are specific to sleep deprivation. I hypothesize that local state transitions are, in fact, a general mechanism, and, furthermore, that all global state transitions are initiated locally and propagated through the cortex. In Aim 1, I will use general anesthesia. General anesthesia and sleep are not the same, but they do share common circuitry within the brain.30-32 Preliminary data from our lab suggests that state transitions under anesthesia can be local, however, no attempt has been made to quantify this observation. In my experiments, I will build upon our published methods to create a continuous measure of brain state independently for each channel of a 3D array of electrodes. In this way, I will be able to identify the initiation of state transitions and track propagation. In Aim 2, I will use the same methods to define brain states and transitions in recordings of natural sleep and wake in freely behaving animals. By recording from the same animals with and without sleep deprivation, I will be able to address whether or not local sleep is specific to sleep deprivation. Collectively, the data collected will allow me to directly address the question of whether local state transitions are a general mechanism that spread to give rise to global state transitions. Regardless of whether sleep and anesthesia show that same results, it is essential to define transitions using the same methodology for comparison and interpretation. My results will have the potential to revolutionize the way the field thinks about sleep and anesthesia which could have profound implication for human patients who suffer from sleep disorders in which they struggle to initiate or maintain natural sleep or the millions of yearly surgical patients. This grant will provide indispensable support for a driven, aspiring scientist in an outststanding environment at the University of Pennsylvania, Perelman School of Medicine. My ultimate career goal is to become an independent researcher investigating the mechanisms of global state transitions.

项目总结