The neuronal circuits of affective itch

情感性瘙痒的神经回路

• 批准号: 10414077
• 负责人: Tasuku Akiyama
• 金额: $ 33.3万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-27 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10414077
• 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; 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; behavioral phenotyping; chronic itch; experimental study; human subject; improved; in vivo; intradermal injection; mouse model; neurochemistry; neuronal cell body; neuronal circuitry; novel strategies; novel therapeutic intervention; optogenetics; parabrachial nucleus; skin disorder; socioeconomics

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和 显著降低了患者的生活质量。大多数慢性瘙痒患者 抱怨瘙痒的不良成分，如被认为是诱因或 止痒增强剂。在这个应用中，我们将研究情感性瘙痒的神经元回路。 在我们的初步数据中，我们已经证实了焦虑的神经元回路被激活(例如， 臂旁外侧核(LPB)、杏仁核、中扣带回(MCC)和内侧核 小鼠皮内注射瘙痒原后的前额叶皮质(MPFC)。目标1将 瘙痒信号杏仁核神经元的解剖和生理特性 采用免疫组织化学法和活体单单位记录法。AIM 2将调查 从LPB到杏仁中央核的投射是否来自 杏仁基底外侧核的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 这些投射的体细胞的光遗传激活。AIM 3将评估是否 光遗传抑制瘙痒信号杏仁核神经元可以恢复瘙痒和焦虑 慢性瘙痒小鼠模型。这种新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以及治疗是否针对 该电路可以改善慢性瘙痒患者的瘙痒和焦虑。

项目成果

Dynorphinergic Projections from the Central Amygdala to the Parabrachial Nucleus Regulate Itch.

从中央杏仁核到臂旁核的强啡能投射调节瘙痒。

• DOI: 10.1523/jneurosci.0726-23.2023
• 发表时间: 2023
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Funahashi,Hideki;Pavlenko,Darya;Sakai,Kent;Verpile,Rebecca;Sanders,KristenM;Akiyama,Tasuku
• 通讯作者: Akiyama,Tasuku