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The neuronal circuits of affective itch

情感性瘙痒的神经回路

基本信息

批准号：
9751771
负责人：
Tasuku Akiyama
金额：
$ 33.64万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-27 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9751771
关键词：
Acute Affective Amygdaloid structure Anatomy Anxiety Behavior Behavioral Bilateral Cations Cell Nucleus Chronic Chronic Disease Clinical Data Distress Economic Burden Electrophysiology (science)Emotions Enhancers Exhibits FOS gene Immunohistochemistry In Situ Hybridization Lateral Lead Light Medial Medical Mus Neurons Neurotransmitters Nociception Pain Pathway interactions Patients Phenotype Physiological Play Population Heterogeneity Prefrontal Cortex Property Proton Pump Pruritus Quality of life Reporting Research Role Signal Transduction Skin Suicide Symptoms Systemic disease Testing anxiety-like behavior anxiety-related behavior base chronic itch experimental study human subject improved in vivo intradermal injection mouse model neurochemistry neuronal cell body neuronal circuitry novel strategies novel therapeutics optogenetics parabrachial nucleus skin disorder socioeconomics

项目摘要

Chronic itch accompanies many skin diseases as well as systemic diseases and significantly decreases patients' quality of life. The majority of patients with chronic itch complain of aversive components of itch such as anxiety that are thought to be triggers or enhancers of itch. In this application, we will investigate the neuronal circuit of affective itch. In our preliminary data, we have confirmed activation of the neuronal circuit for anxiety (e.g., lateral parabrachial nucleus (LPB), amygdala, midcingulate cortex (MCC), and medial prefrontal cortex (mPFC)) following intradermal injection of pruritogens in mice. Aim 1 will characterize anatomical and physiological properties of itch-signaling amygdala neurons using immunohistochemistry as well as in vivo single unit recording. Aim 2 will investigate whether the projections from the LPB to the central nucleus of the amygdala and from the mPFC and MCC to the basolateral amygdala modulate itch and anxiety. Behavioral and electrophysiological properties of these amygdala neurons will be determined during optogenetic activation of somata of these projections. Aim 3 will evaluate whether optogenetic inhibition of itch-signaling amygdala neurons can recover itch and anxiety in a mouse model of chronic itch. This novel approach would give us important information about the role of the affective itch circuit in chronic itch and whether treatments that target the circuit could improve both itch and anxiety in chronic itch patients.

慢性瘙痒伴随许多皮肤病以及全身性疾病，严重降低了患者的生活质量。大多数慢性瘙痒患者抱怨瘙痒的厌恶成分，如焦虑，被认为是触发器或瘙痒增强剂在这个应用程序中，我们将研究情感性瘙痒的神经回路。在我们的初步数据中，我们已经证实了焦虑的神经元回路的激活（例如，外侧臂旁核（LPB）、杏仁核、中扣带回皮质（MCC）和内侧前额叶皮层（mPFC））。目标1将表征瘙痒信号杏仁核神经元的解剖学和生理学特性使用免疫组织化学以及体内单个单元记录。目标2将调查是否LPB到杏仁核中央核的投射和LPB到杏仁核中央核的投射基底外侧杏仁核的mPFC和MCC调节瘙痒和焦虑。行为和这些杏仁核神经元的电生理特性将在这些投射的胞体的光遗传学激活。目标3将评估是否对瘙痒信号传导杏仁核神经元的光遗传学抑制可以恢复瘙痒和焦虑，慢性瘙痒小鼠模型。这种新颖的方法将为我们提供重要的信息关于情感瘙痒回路在慢性瘙痒中的作用，该电路可以改善慢性瘙痒患者的瘙痒和焦虑。