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Adolescent alcohol drinking and GABA signaling

Adolescent alcohol drinking and GABA signaling
青少年饮酒和 GABA 信号传导
批准号:
9913434
负责人:
Kevin J Bender
金额:
$39.98万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-04-12 至 2024-03-31

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中文摘要
翻译
项目摘要 青春期标志着一个增加冒险和探索的时期。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 在以后的生活中出现紊乱。青春期前额叶皮层成熟的一个主要部位是GABA能抑制 神经元,包括小清蛋白阳性枝形细胞。枝形细胞直接与轴突形成突触 邻近的多巴胺能锥体细胞的潜在起始位点。因此,他们是独一无二的, 调节锥体细胞尖峰。在这里,我们的目标是了解这两种抑制性细胞的功能如何, 类受青少年饮酒,并确定是否操纵氯化物 转运体功能改变饮酒行为。我们将结合电生理学和双光子 成像以了解如何在细胞水平上调节中间神经元功能,以及病毒操纵 氯转运体功能与行为配对,以了解前额叶抑制功能如何调节 喝酒这项研究的结果将提供深入了解如何抑制电路有助于饮酒行为 并且可以阐明治疗酒精滥用障碍的潜在治疗靶点。
英文摘要
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.
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