权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Norepinephrine tunes prefrontal-thalamic circuitry to modulate avoidance behavior

去甲肾上腺素调节前额丘脑回路以调节回避行为

基本信息

批准号：
10586051
负责人：
Wen-Jun Gao
金额：
$ 18.59万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-03-07 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10586051
关键词：
Address Adrenergic Agents Affect Amygdaloid structure Animal Behavior Animal Model Animals Anti-Anxiety Agents Anxiety Anxiety Disorders Arousal Attention Behavior Behavioral Behavioral Assay Brain region CAV2 gene Calcium Cell Nucleus Clinical Communication Data Analyses Decision Making Detection Dopamine-beta-monooxygenase Dorsal Emotional Enterobacteria phage P1 Cre recombinase Environment Equilibrium Exhibits Female Fiber Fright G-Protein-Coupled Receptors Genetic Hippocampus Image Imaging Device Insula of Reil Major Depressive Disorder Medial Mediating Mental disorders Methods Monitor Moods Morphology Motivation Mus Neurons Neurotransmitters Norepinephrine Pathway interactions Photometry Pilot Projects Play Population Post-Traumatic Stress Disorders Posture Prefrontal Cortex Process Receptor Activation Reporting Rewards Risk Taking Rodent Role Schizophrenia Signal Transduction Stress Testing Thalamic structure Time Varicosity Video Recording Viral Virus Wakefulness addiction anxiety-like behavior approach avoidance behavior arm avoidance behavior brain dysfunction common symptom density designer receptors exclusively activated by designer drugs disabling symptom executive function flexibility improved in vivo innovation locus ceruleus structure male millisecond neural neural circuit neuromechanism noradrenergic optogenetics particle response sensor spatiotemporal temporal measurement

项目摘要

Norepinephrine tunes prefrontal-thalamic circuitry to modulate avoidance behavior Abstract Anxiety disorders are the most common mental illness in the U.S., affecting ~18% of the population. However, the underlying mechanisms associated with anxiety remain elusive. Recent evidence has identified the medial prefrontal cortex (mPFC) as a crucial regulator of anxiety and disruption of mPFC-mediated executive functions in anxiety disorders. On the other hand, norepinephrine (NE) has long been associated with stress and anxiety. A morphological study showed a higher density of dopamine beta-hydroxylase (DBH) varicosities in the PFC than in other cortices. However, how the mPFC executes top-down control over other brain regions to regulate anxiety-related approach-avoidance behavior and whether and how this is modulated by norepinephrine (NE) remain unclear. This project will test the innovative concept that mPFC – paraventricular thalamus (mPFC-PVT) circuit is an important previously overlooked target for anxiety and decision-making. Our pilot study suggests that chemogenetically inhibiting mPFC-PVT pathway with DREADD viral victor significantly increased the time spent in the open arm of the elevated plus-maze, indicating a reduction in anxiety-related avoidance behavior. We thus hypothesize that mPFC-pPVT neurons are active during the exploration of aversive environments, which drives avoidance behavior and elicits anxiety-dependent behaviors. We will explore the extent that prefrontal NE signaling modulates this effect. We will investigate the communication between these two regions by using calcium imaging, a detailed DeepLabCut analysis of animal’s behavior (Aim 1) combined with a G- protein-coupled receptor (GPCR) Activation-Based Norepinephrine (GRAB-NE) sensor (Aim 2) for anxiety-like behavior. The GRAB-NE will allow us to monitor prefrontal NE dynamics in real-time in free-behaving animals. The DeepLabCut™ will provide a detailed analysis of an animal’s posture with a sub-millisecond temporal resolution that could be used to determine an animal’s emotional state change. In summary, we address these conceptually innovative questions using state-of-the-art methods, which allow for precise, causal interrogation into the role of this circuit both in vivo and ex vivo in a projection-specific manner.

去甲肾上腺素调节前额叶-丘脑回路来调节回避行为