Role of Basal Forebrain Neurons in Sleep-Wake States

基底前脑神经元在睡眠-觉醒状态中的作用

基本信息

批准号：
7884456
负责人：
BARBARA E JONES
金额：
$ 18.01万
依托单位：
MCGILL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2000
资助国家：
美国
起止时间：
2000-07-06 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7884456
关键词：
Acetylcholine Alzheimer&apos s Disease Arousal Attention Auditory Behavior Behavioral Calcium-Binding Proteins Carrier Proteins Cells Cerebral cortex Chemicals Discrimination Disease Drowsiness Electrophysiology (science)Fire - disasters Functional disorder Glutamates Goals Grant Head Human Hypothalamic structure Immunohistochemistry Inhibitory Synapse Knowledge Label Lead Learning Muscle Tonus Narcolepsy Neuroanatomy Neurofilament Proteins Neurons Play Population Process Proteins Psychological reinforcement Quinine REM Sleep Rattus Relative (related person)Research Research Personnel Role Skeletal muscle structure of neck Sleep Slow-Wave Sleep Staining method Stains Stimulus Sucrose Synapses System Techniques aversive conditioning basal forebrain basal forebrain cholinergic neurons behavior test cholinergic cholinergic neuron gamma-Aminobutyric Acid gephyrin insight nervous system disorder novel postsynaptic presynaptic programs rapid eye movement relating to nervous system sensory stimulus

项目摘要

DESCRIPTION (provided by applicant): The long term goal of the research is to elucidate the neural and chemical mechanisms generating sleep- wake states and regulating cortical activity and behavior across those states. Such understanding will illuminate how neurological diseases, such as Alzheimer's, or sleep-wake disorders, such as narcolepsy, result in loss of attention and/or the ability to maintain an aroused, waking state. The proposed studies focus upon the role of cholinergic, GABAergic and newly discovered glutamatergic neurons in the basal forebrain (BF). Using juxtacellular labeling of neurons recorded in unanesthetized, head-fixed rats, the discharge of immunohistochemically identified cells will be characterized in association with electroencephalographic (EEG) activity recorded from the cortex and electromyographic (EMG) activity recorded from postural neck muscles across the states of waking, slow wave sleep (SWS) and paradoxical sleep (PS, also known as rapid eye movement sleep, REMS, in humans). Applying newly developed behavioral testing, previously identified W/PS-active, cholinergic BF neurons will be examined for their discharge in association with attention and cortical activation during waking. GABAergic BF neurons will be further studied for their discharge in association with sleep, as SWS or SWS/PS-active cells, and in reciprocal relation to the cholinergic cells in attentional tasks. The unique role of glutamatergic BF neurons will be characterized in relation to cortical activity, behavioral arousal and attention or reinforcement. By neuroanatomical tracing combined with immunohistochemistry for presynaptic vesicular transporter proteins and postsynaptic proteins, projections and synaptic connections of BF cholinergic, GABAergic and glutamatergic neurons will be delineated onto target neurons in the cerebral cortex. Collectively, these studies will elucidate how specific basal forebrain cell groups can promote attention along with cortical activation or behavioral arousal and others reciprocally dampen these processes to evoke drowsiness and sleep. They will provide insight into how imbalances in these systems could lead to deficits in attention and arousal as well as disruption of sleep-wake states.

描述（由申请人提供）：该研究的长期目标是阐明产生睡眠状态的神经和化学机制，并调节这些状态的皮质活动和行为。这种理解将阐明神经系统疾病（例如阿尔茨海默氏症或睡眠障碍）如何导致关注和/或维持唤醒，清醒状态的能力丧失。拟议的研究集中于胆碱能，GABA能和新发现的谷氨酸能神经元在基础前脑（BF）中的作用。使用在未经麻醉的，头部固定的大鼠中记录的神经元的并置标记，免疫组织化学上鉴定的细胞的排放将与来自皮层和电疗法和电疗法（EMG）活性（EMG）活性记录的电脑电图（EEG）活性相关。 Rems，在人类中）。将检查新开发的行为测试，先前鉴定出的带有PS活性的，胆碱能BF神经元将与醒来过程中的注意力和皮质激活有关。将进一步研究GABA能BF神经元与睡眠相关，作为SWS或SWS/PS活性细胞以及注意力任务中与胆碱能细胞的相互关系。谷氨酸能BF神经元的独特作用将与皮质活性，行为唤醒和注意力或增强有关。通过神经解剖学跟踪，与免疫组织化学结合了免疫组织化学，用于突触前囊泡转运蛋白和突触后蛋白，BF胆碱能，Gabaergic和Glutamatergic神经元的投影和突触连接，将在塞氏骨中的靶神经元中绘制为靶神经元。总的来说，这些研究将阐明特定的基础前脑细胞基团如何促进注意力以及皮质激活或行为唤醒等，以及其他相互抑制的这些过程，以引起嗜睡和睡眠。他们将洞悉这些系统中的失衡如何导致注意力和唤醒以及睡眠效果状态的破坏。