Parabrachial nucleus control of arousal

 描述（由申请人提供）：我们先前的损伤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，我们假设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）。在这项拨款提案中，我们将应用一种新的方法化学遗传学（或DREADD）选择性地激活PB中的神经元，它们向视前区，后外侧下丘脑（pLH），基底前脑（BF）和丘脑的投射，并检查和确定每个投射在调节PB控制皮质唤醒和觉醒中的作用。在具体目标1中，我们将测试PB激活对觉醒的影响。在具体目标2中，我们将研究PB重复激活所产生的长时间觉醒和高睡眠压力对睡眠-觉醒回路和睡眠反弹的影响。在具体目标3中，我们将选择性地刺激PB-BF、PB-视前区、PB-pLH和PB-丘脑的通路，并分析哪种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和延髓睡眠中心，面旁带（PZ）之间的相互作用。我们假设PB抑制PZ。这种抑制作用是通过红核后野（RRF）中的GABA能神经元实现的。这种抑制作用与先前发现的PZ抑制PB一起，形成了调节睡眠-觉醒行为的共抑制回路。

 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.