Adolescent alcohol drinking and GABA signaling

青少年饮酒和 GABA 信号传导

基本信息

批准号：
10377453
负责人：
Kevin J Bender
金额：
$ 41.49万
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：
2019-04-12 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10377453
关键词：
AKT Signaling Pathway Acute Adolescence Adolescent Adult Affect Age Alcohol abuse Alcohol consumption Alcohol dependence Alcohols Axon Behavior Behavioral Brain Cell physiology Cells Chlorides Complement Data Decision Making Development Disease Electrophysiology (science)Etiology Executive Dysfunction Exploratory Behavior Functional disorder Glutamates Goals Heavy Drinking Image Individual Interneuron function Lead Life Long-Term Effects Maintenance Mediating Molecular Mus Myoepithelial cell Neurons Optics PI3K/AKT Parvalbumins Pattern Perinatal Pharmacology Prefrontal Cortex Principal Investigator Property Proto-Oncogene Proteins c-akt Pyramidal Cells RNA Interference Regulation Risk Assessment Risk-Taking Rodent Signal Transduction Site Slice Substance abuse problem Synapses Techniques Testing Therapeutic Intervention Time Viral Work adolescent alcohol exposure alcohol effect alcohol risk alcohol use disorder cellular targeting combat critical period drinking drinking behavior executive function gamma-Aminobutyric Acid infancy inhibitory neuron insight mature animal nervous system disorder new therapeutic target novel therapeutic intervention periadolescent postsynaptic postsynaptic neurons prevent problem drinker sodium-potassium-chloride cotransporter 1 protein synaptic function therapeutic target two-photon underage drinking

项目摘要

PROJECT SUMMARY Adolescence marks a period of increased risk taking and exploration. As part of this exploratory behavior, many individuals initiate alcohol use during adolescence, which can lead to increased risk for alcohol use disorders later in life. One major site of adolescent maturation in prefrontal cortex are GABAergic inhibitory neurons, including parvalbumin positive chandelier cells. Chandelier cells synapse directly onto the axon potential initiating sites of neighboring glutamatergic pyramidal cells. They are therefore uniquely poised to regulate pyramidal cell spiking. Here, our goal is to understand how the function of these two inhibitory cell classes are affected by adolescent alcohol consumption, and to determine if manipulations to chloride transporter function alters drinking behavior. We will use a combination of electrophysiology and 2-photon imaging to understand how interneuron function is regulated at the cellular level, and viral manipulation of chloride transporter function paired with behavior to understand how prefrontal inhibitory function regulates drinking. Results of this study will provide insight into how inhibitory circuits contribute to drinking behavior and may elucidate potential therapeutic targets to treat alcohol abuse disorders.

项目概要青春期标志着冒险和探索增加的时期。作为这种探索行为的一部分，许多人在青春期开始饮酒，这可能导致饮酒风险增加以后生活中的疾病。前额皮质青少年成熟的一个主要部位是 GABA 能抑制神经元，包括小白蛋白阳性吊灯细胞。枝形吊灯细胞突触直接连接到轴突上邻近谷氨酸能锥体细胞的潜在起始位点。因此，他们有独特的准备调节锥体细胞尖峰。在这里，我们的目标是了解这两种抑制细胞的功能如何课程受到青少年饮酒的影响，并确定是否对氯化物进行了操纵转运蛋白功能改变饮酒行为。我们将结合使用电生理学和 2 光子成像以了解中间神经元功能如何在细胞水平上受到调节，以及病毒操作氯转运蛋白功能与行为相结合，以了解前额叶抑制功能如何调节喝。这项研究的结果将深入了解抑制回路如何影响饮酒行为并可能阐明治疗酒精滥用疾病的潜在治疗靶点。