Dissecting Monoaminergic Physiology of Prefrontal Cortical Astrocytes

剖析前额皮质星形胶质细胞的单胺能生理学

基本信息

批准号：
9912149
负责人：
Kira Poskanzer
金额：
$ 20.16万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-15 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9912149
关键词：
Acute Address Amphetamines Animal Behavior Astrocytes Attention Behavior Behavioral Biological Brain Brain region CRISPR/Cas technology Cells Data Detection Dopamine Drug Exposure Exposure to Feedback Functional disorder Future Genes Genetic Genetic Transcription Glutamates Goals Heterogeneity Image Intervention Learning Literature Long-Term Effects Measures Medial Mediating Mediator of activation protein Mental disorders Modeling Motivation Neuroglia Neuromodulator Neuronal Plasticity Neurons Neurotransmitters Norepinephrine Outcome Output Pharmaceutical Preparations Physiological Physiology Play Population Population Dynamics Positioning Attribute Prefrontal Cortex Protocols documentation Psychostimulant dependence Regulation Research Research Support Rewards Role Scheme Serotonin Signal Transduction Signaling Protein Substance Use Disorder Synaptic Transmission System Testing Work addiction brain behavior cell type drug action drug of abuse experimental study extracellular monoamine motivated behavior nervous system disorder neural circuit neuroadaptation neurobehavioral nigrostriatal pathway photoactivation psychostimulant relating to nervous system response signal processing spatiotemporal two-photon

项目摘要

PROJECT SUMMARY Motivated behaviors, included those altered in substance use disorders, are known to be regulated by monoaminergic circuits (containing neurons that release dopamine, serotonin, and norepinephrine) in multiple brain regions. Disentangling these circuits from the cell-level to the systems- and behavioral-levels has almost exclusively been limited to studying the physiology of neurons. However, recent data suggest that the activity of a non-neuronal cell type—astrocytes—may have profound effects on how monoaminergic networks function, but how astrocytes respond to monoamines and change their physiology in response to repetitive drug exposure remain almost completely unstudied. The current proposal aims to address gaps in our understanding of addiction, monoamine signaling, and multi-cell type population dynamics by uncovering fundamental cell biological signaling systems in astrocytes that are critical for the function of brain regions with monoaminergic input. In Aim 1, we will use two-photon imaging and photoactivation to interrogate the cell signaling mechanisms that prefrontal cortical astrocytes deploy to sense extracellular monoamine dynamics across cortical layers. In Aim 2, we will decode the mechanisms by which astrocytes change, both instrinsically and in their output to the neuronal population, after long-term exposure to a psychostimulant. With these aims, we will probe the roles of astrocyte physiology in baseline prefrontal cortex function and as mediators of circuit neuroplasticity in a model of addiction.

项目摘要已知有动机行为，包括在药物使用障碍中改变的行为，已知受多巴胺中的单胺能回路（包含释放多巴胺，5-羟色胺和去甲肾上腺素的神经元）大脑区域。将这些电路从细胞级拆开到系统和行为级别几乎具有仅限于研究神经元的生理学。但是，最近的数据表明该活动非神经元细胞类型（腹膜细胞）可能对单胺能网络的功能有深远的影响，但是，星形胶质细胞如何对单胺反应并改变其生理学，以应对重复性药物接触几乎完全没有研究。当前的提议旨在解决我们的差距通过发现成瘾，单胺信号传导和多细胞类型人群动力学的理解星形胶质细胞中的基本细胞生物学信号系统对于大脑区域的功能至关重要单胺能输入。在AIM 1中，我们将使用两光子成像和光激活来询问细胞信号机制那个前额叶皮质星形胶质细胞部署，以感知皮质层的细胞外单胺动力学。在 AIM 2，我们将解码星形胶质细胞在工具上和输出中改变的机制长期暴露于心理刺激剂后，神经元种群。以这些目的，我们将调查基线前额叶皮层功能中的星形胶质细胞生理学和作为模型中电路神经塑性的介体成瘾。