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In Vivo Two-Photon Imaging of Cortical Activity in Alcohol-Dependent Mice

酒精依赖小鼠皮质活动的体内双光子成像

基本信息

批准号：
8635067
负责人：
JOHN J. WOODWARD
金额：
$ 21.49万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-03-15 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8635067
关键词：
Affect Alcohol abuse Alcohol consumption Alcohol dependence Alcoholism Alcohols Behavior Blood Vessels Blood flow Brain Brain imaging Breeding Calcium Caliber Cells Cerebrum Chronic Cognition Cognitive Complication Coupling Cues Dependence Diffusion Dyes Economic Burden Electroencephalography Ethanol Ethanol dependence Experimental Models Future Glutamates Goals Heavy Drinking Image Impairment In Vitro Individual Interneurons Intervention Label Laser Scanning Microscopy Lead Light Maps Measures Medial Methods Modeling Molecular Monitor Morbidity - disease rate Mouse Strains Mus Neurobiology Neuroglia Neurons Population Prefrontal Cortex Preparation Process Property Proteins Relapse Reliance Reporting Research Design Resolution Rest Sensory Sensory Process Signal Transduction Slice Specificity Stimulus System Techniques Testing Thinking Tissue Sample Tissues Toxic effect Visible Radiation Visual Visual Cortex Withdrawal alcohol cue alcohol effect alcohol research arteriole base cell type cerebrovascular drinking fluorophore hippocampal pyramidal neuron in vivo light microscopy mortality mouse model new technology novel novel strategies prevent problem drinker public health relevance response selective expression sensor treatment strategy two-photon vapor visual stimulus

项目摘要

The goal of this project is to use in vivo two-photon laser scanning microscopy (2PLSM) to examine changes in neuronal activity in ethanol-dependent mice. Chronic drinking that leads to dependence is associated with marked changes in brain function including impairments in cortical processing and cognition. These impairments likely underlie the transition to heavy drinking and elucidating the mechanisms that underlie these changes is critical towards developing treatments and interventions that restore control over behavior. A key limitation in the study of the mechanistic actions on alcohol on brain function is the reliance upon in vitro techniques to monitor neuronal function. These approaches, while extremely valuable, are hindered by the loss of relevant sensory input and disruption of normal circuitry during preparation of the in vitro tissue sample. While brain imaging approaches can avoid this complication, they are compromised by a lack of specificity with regard to spatial resolution and neuronal sub-type. In this application, we will use in vivo 2PLSM to image neuronal activity and neurovascular function in alcohol-dependent mice. In Aim 1, we will utilize a recently developed line of mice that, when crossed with a specific Cre-driver mouse line, expresses the calcium-sensor protein GCaMP3 in a defined sub-population of neurons. Neuronal calcium dynamics will be monitored in glutamatergic pyramidal neurons and fast-spiking interneurons by crossing the GCaMP3 mice with the Wfs1-Tg2-CreERT2 line and Pvalb-2A-Cre line; respectively. Activity will be monitored both during rest and during presentation of visual cues that reliably induce activity in visual cortex neurons. In Aim 2, neurovascular coupling (e.g., activity-dependent changes in local brain blood flow) will be monitored by the use of a dye recently shown by the Co-I to effectively signal changes in arteriolar blood flow. Together, results from these two complementary aims will establish the technique of in vivo 2PLSM in the study of alcohol action and will support future studies designed to analyze the effects of alcohol on cortical function.

本项目的目标是使用体内双光子激光扫描显微镜（2PLSM）