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.

项目摘要青春期标志着冒险和勘探增加的时期。作为这种探索行为的一部分，许多人在青春期开始使用饮酒，这可能导致饮酒风险增加后来的疾病。前额叶皮层中青春期成熟的一个主要部位是GABA能抑制神经元，包括白蛋白阳性吊灯细胞。吊灯直接突触到轴突邻近谷氨酸能锥体细胞的潜在启动部位。因此，他们被独特地准备调节锥体细胞峰值。在这里，我们的目标是了解这两个抑制性细胞的功能课程受青少年饮酒的影响，并确定是否对氯化物进行操作转运蛋白功能改变饮酒行为。我们将结合电生理学和2光子成像以了解如何在细胞水平调节中间神经元功能，并对氯化物转运蛋白功能与行为配对，以了解前额叶抑制功能如何调节喝。这项研究的结果将提供有关抑制回路如何促进饮酒行为的见解并可能阐明潜在的治疗靶标以治疗酗酒障碍。