Parabrachial nucleus control of arousal

臂旁核控制觉醒

基本信息

批准号：
9883050
负责人：
JUN LU
金额：
$ 37.84万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9883050
关键词：
Affect Anatomy Animals Applications Grants Arousal Behavior Bilateral Brain Stem Cells Cerebral cortex Clozapine Coma Conscious Data Electrodes Electroencephalography Glutamates Goals Histamine Histology Hour Hypothalamic structure Implant Injections Label Lateral Lesion Medial Mediating Mus Muscarinic M3 Receptor Neural Pathways Neurons Oxides Pathway interactions Pontine structure Preoptic Areas Property Prosencephalon Rattus Regulation Role Saline Signal Transduction Sleep Structure System Testing Thalamic structure Tracer Wakefulness basal forebrain basal forebrain cholinergic neurons base cholinergic designer receptors exclusively activated by designer drugs hypocretin locus ceruleus structure neural circuit non rapid eye movement novel strategies parabrachial nucleus pressure public health relevance retrograde transport vector

项目摘要

DESCRIPTION (provided by applicant): Our previous lesion and tracing studies identify the parabrachial nucleus (PB) as the key structure in the brainstem for cortical arousal and wakefulness and we hypothesize that the PB is the key structure of ascending reticular activating system (ARAS). We further show that PB, via the basal forebrain (BF) not the thalamus, regulates cortical arousal (consciousness). In this grant proposal, we will apply a novel approach chemogenetics (or DREADD) to selectively activate the neurons in the PB, their projections to the preoptic, posterior lateral hypothalamus (pLH), basal forebrain (BF) and thalamus and examine and identify the role of each projection in mediating the PB control in cortical arousal and wakefulness. In Specific Aim 1, we will test the effect of PB activation on wakefulness. In Specific Aim 2, we will examine the effects of long wakefulness and high sleep pressure produced by repeat activation of the PB on sleep-wake circuits and sleep rebound. In Specific Aim 3, we will selectively stimulate the pathways of PB-BF, PB-preoptic, PB-pLH and PB-thalamus and dissect which pathway is involved in regulation cortical arousal or general wakefulness. In Specific Aim 4, we will investigate the interaction between the PB and medullary sleep center, parafacial zone (PZ). We hypothesize that the PB inhibits PZ. This inhibition is via the GABAergic neurons in the retrorubral field (RRF). This inhibition, together with previous finding that PZ inhibits the PB, forms co-inhibitory circuit that regulates sleep-wake behavior.

描述（申请人提供）：我们之前的病变和追踪研究确定臂旁核（PB）是脑干中皮质唤醒和觉醒的关键结构，并且我们追求PB是上行网状激活系统（ARAS）的关键结构我们进一步表明，PB 通过基底前脑 (BF) 而不是丘脑调节皮质唤醒（意识）。方法化学遗传学（或 DREADD）选择性地激活 PB 中的神经元及其对视前、后外侧下丘脑 (pLH)、基底前脑 (BF) 和丘脑的投射，并检查和识别每个投射在介导 PB 控制中的作用在特定目标 1 中，我们将测试 PB 激活对觉醒的影响。在特定目标 2 中，我们将检查长时间觉醒和觉醒的影响。睡眠-觉醒回路上 PB 的重复激活和睡眠反弹所产生的高睡眠压力在具体目标 3 中，我们将选择性地刺激 PB-BF、PB-视前、PB-pLH 和 PB-丘脑通路，并剖析是哪个通路。参与调节皮质唤醒或一般觉醒。在具体目标 4 中，我们将研究 PB 和髓质睡眠中枢、面旁区 (PZ) 之间的相互作用。 PB 抑制 PZ。这种抑制是通过红核后区 (RRF) 中的 GABA 能神经元实现的。这种抑制与之前发现的 PZ 抑制 PB 一起，形成了调节睡眠-觉醒行为的共抑制回路。