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.

项目摘要长期以来，睡眠使科学家和哲学家着迷。迄今为止，睡眠场已变得巨大迈向解释如何产生在睡眠阶段记录的活动模式的大步。但是，清醒和睡眠之间以及睡眠阶段之间的过渡是可以理解的。睡觉和促进神经元种群暴露了自我激发和相互抑制12-16，这被认为是给予的达到胜利者的策略。17,18通常认为这意味着唤醒和睡眠状态无法在大脑中共存。但是，从几个专业类的物种中半球睡眠，我们知道一部分大脑有可能入睡，而另一个遗骸可能醒着。18,19,21,22在大鼠记录的局部睡眠发作中，皮质组织的空间限制袋在行为清醒期间输入了活动的慢波节奏。23我们的实验室和其他实验室已经证明皮质中的这种活动也在全身麻醉期间经历状态转变。27,28剩下的未知是地方国家过渡是否是意识之间过渡的一般机制和无意识或特定于睡眠剥夺。我假设当地国家过渡实际上，这是一种一般机制，此外，所有全球状态过渡均在本地启动并通过皮质传播。在AIM 1中，我将使用全身麻醉。全身麻醉和睡眠是不一样的，但它们确实在大脑中共享通用电路。30-32我们实验室的初步数据表明在麻醉下进行状态转变可以是局部的，但是，没有尝试量化这个观察结果。在我的实验中，我将基于我们已发表的方法来创建一个连续的度量大脑状态独立于3D电极阵列的每个通道。这样，我将能够确定启动国家过渡和跟踪传播。在AIM 2中，我将使用相同的方法来定义大脑状态以及自然睡眠记录的过渡和自由表现的动物唤醒。通过从同一录制有或没有睡眠不足的动物，我将能够解决当地睡眠是否特定睡眠剥夺。总体而言，收集的数据将使我直接解决了是否本地的问题国家过渡是一种传播以引起全球国家过渡的一般机制。不管睡眠和麻醉是否显示出相同的结果，必须使用相同的过渡定义过渡比较和解释的方法。我的结果将有可能改变田野思考睡眠和麻醉，这可能对患者的人类患者产生深远影响从他们努力发起或保持自然睡眠或数百万年度手术的睡眠障碍中患者。这笔赠款将为驱动器提供必不可少的支持，有抱负的科学家宾夕法尼亚大学佩雷尔曼医学院的环境。我的最终职业目标是成为研究全球国家过渡机制的独立研究人员。