Parabrachial nucleus control of arousal

臂旁核控制觉醒

• 批准号: 9251920
• 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
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9251920
• 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; Injectable; Injection of therapeutic agent; 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; hypocretin; locus ceruleus structure; neural circuit; novel strategies; parabrachial nucleus; pressure; public health relevance; retrograde transport; vector

 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（由适用提供）：我们以前的病变和追踪研究确定副核（PB）是皮质唤醒和觉醒的脑干中的关键结构，我们假设PB是上升网状激活系统（ARAS）的关键结构。我们进一步表明，通过基本前脑（BF）而不是丘脑，PB调节皮质唤醒（意识）。在这项赠款建议中，我们将采用一种新颖的化学遗传学（或dreadd）来选择性地激活PB中的神经元，其项目将其投向前，后外侧下丘脑（PLH），基本前脑（BF）和丘脑，并检查和检查和确定和确定PB对照在Cortical cortal and wake and Wake and Wake的作用。在特定目标1中，我们将测试PB激活对清醒的影响。在特定的目标2中，我们将研究通过PB重复激活睡眠觉醒电路和睡眠反弹产生的长清醒和高睡眠压力的影响。在特定的目标3中，我们将有选择地刺激PB-BF，PB-Preoptic，PB-PLH和PB-Thalamus的途径，并剖析哪些途径参与调节皮质唤醒或一般清醒。在特定的目标4中，我们将研究PB和髓质睡眠中心（PZ）之间的相互作用。我们假设PB抑制了PZ。这种抑制是通过腹部后场（RRF）中的GABA能神经元进行的。这种抑制作用与以前的发现PZ抑制PB一样，形成了调节睡眠效果行为的共抑制作用。