Adolescent alcohol drinking and GABA signaling

项目总结 青春期标志着冒险和探索的增加。作为这种探索行为的一部分， 许多人在青春期就开始饮酒，这可能导致饮酒风险增加。 在以后的生活中会有障碍。青少年前额叶皮质成熟的一个主要部位是GABA能抑制 神经元，包括小白蛋白阳性的吊灯细胞。吊灯细胞直接突触到轴突上 邻近谷氨酸能锥体细胞的潜在起始点。因此，他们独一无二地准备好 调节锥体细胞的尖峰活动。在这里，我们的目标是了解这两个抑制细胞的功能是如何 班级受到青少年饮酒的影响，并确定是否操纵氯离子 转运蛋白功能改变饮酒行为。我们将使用电生理学和双光子的组合 成像以了解中间神经元功能是如何在细胞水平上调节的，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。这项研究的结果将对抑制回路如何影响饮酒行为提供深入的见解 并可能阐明治疗酒精滥用障碍的潜在治疗靶点。

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.