Neuronal mapping of anxiety and panic

焦虑和恐慌的神经元图谱

• 批准号: 9294861
• 负责人: Luis De Lecea
• 金额: $ 40.49万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-22 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9294861
• 关键词: Acute; Amygdaloid structure; Anatomy; Anxiety; Anxiety Disorders; Area; Arousal; Behavior; Behavioral; Brain Stem; Cardiovascular system; Cell Nucleus; Cells; Chronic; Corticosterone; Data; Disease; Freezing; Fright; Functional disorder; Goals; High Prevalence; Hypothalamic structure; Lateral; Lead; Link; Maps; Measures; Mediating; Mental Depression; Mental disorders; Mus; Neural Pathways; Neurons; Neurotransmitters; Norepinephrine; Panic; Panic Attack; Panic Disorder; Pathology; Pathway interactions; Patients; Physiological; Prevalence; Recurrence; Specificity; Stimulus; Structure of terminal stria nuclei of preoptic region; Sum; Symptoms; Testing; anatomical tracing; behavioral response; depressive symptoms; effective therapy; experimental study; hypocretin; improved outcome; neuronal circuitry; optogenetics; paraventricular nucleus; public health relevance; respiratory; response; stressor; tool; treatment of anxiety disorders

DESCRIPTION (provided by applicant): Panic disorder is a common psychiatric illness with a lifetime prevalence of about 4.5%. The hallmark of the disorder is recurring panic attacks, which can appear suddenly and unexpectedly, consisting of pronounced fear, as well as cardiovascular and respiratory responses. The initial pathology in these patients appears to be an alteration somewhere in the central neural pathways regulating normal panic responses, thus rendering the patients susceptible to unprovoked panic symptoms when exposed to ordinarily mild interoceptive stressors. Understanding the neuronal underpinnings of panic attacks would significantly improve the outcomes and treatment. The neurotransmitter hypocretin (Hcrt), also known as orexin, has been recently linked to hyperarousal, anxiety and panic, but the specific effector circuits are unknown. Anatomical and functional evidence suggests that one of the possible Hcrt/orexin targets are norepinephrine (NE)-containing neurons in the brainstem. Here, we will test the overall hypothesis that Hcrt/orexin acts through ventral norepinephrine A2 neurons and their efferents to produce different components of the anxiety and panic responses. We will use anatomical tracing and optogenetic tools to obtain a functional map of the neuronal circuitry connecting A2 neurons with several of its anatomical targets, namely the paraventricular hypothalamic nucleus (PVN) and the bed nucleus of the stria terminalis (BNST). We will also determine the connectivity between these circuits and the arousal promoting Hcrt/orexin neurons in the lateral hypothalamus. Our experiments will increase our understanding of the circuitry associated with anxiety with cellular specificity and may lead to potentially more selective treatments for anxiety and panic disorders.

描述(申请人提供)：惊恐障碍是一种常见的精神疾病，终生患病率约为4.5%。这种疾病的特征是反复发作的恐慌症，这种恐慌症可能会突然、意外地出现，包括明显的恐惧以及心血管和呼吸系统反应。这些患者最初的病理似乎是调节正常恐慌反应的中枢神经通路的某个地方发生了变化，从而使患者在暴露于通常温和的感觉间应激源时容易出现无端的恐慌症状。了解恐慌症发作的神经基础将显著改善结果和治疗。神经递质下丘脑肌素(Hcrt)，也被称为增食欲素，最近被认为与过度唤醒、焦虑和恐慌有关，但具体的效应电路尚不清楚。解剖学和功能证据表明，Hcrt/增食欲素可能的靶点之一是脑干中含有去甲肾上腺素(NE)的神经元。在这里，我们将检验Hcrt/增食欲素通过腹侧去甲肾上腺素A2神经元及其传出产生焦虑和恐慌反应的不同成分的总体假设。我们将使用解剖示踪和光遗传学工具来获得连接A2神经元与其几个解剖目标，即下丘脑室旁核(PVN)和终纹床核(BNST)的神经元回路的功能图。我们还将确定这些回路与觉醒促进下丘脑外侧区Hcrt/增食欲素神经元之间的联系。我们的实验将增加我们对与焦虑相关的具有细胞特异性的回路的理解，并可能导致对焦虑和恐慌症的更具选择性的治疗。