Investigation of a novel prelimbic cortical peptidergic population in binge drinking behavior

项目摘要 酒精使用障碍(AUD)是一种慢性脑部疾病，引起重大的健康和社会问题 比任何其他类型的药物滥用死亡人数都要多。在所有形式的酒精滥用中，酗酒是 最常见、最昂贵、最致命的过度饮酒模式。解决这一重大公共卫生问题 需要对酗酒的潜在神经生物学有更好的理解。一个特殊的地区 狂饮的兴趣是大脑皮层(PL)。我们之前已经证明了兴奋性和抑制性 在酒精暴露的各种模型之后，PL中的信号会发生变化。另外，我们的初步数据 提示PL内的生长抑素神经元与酗酒有关。这是 尤其新颖，因为它代表了一个有希望的神经元群体，能够减少酗酒行为。 我们的项目将(1)研究PL生长抑素神经元如何与其他神经元相互作用(突触连接 和信号)，以及(2)它们在酗酒中扮演什么角色(化学生成激活和抑制)。已被占用 总之，这些实验将评估这样一种假设，即PL中的生长抑素神经元是一种有希望的 酒精使用障碍的治疗目标，特别是酗酒。

Project Summary Alcohol Use Disorder (AUD) is a chronic brain disease with major health and societal concerns resulting in more deaths than any other type substance misuse. Of all the forms of alcohol misuse, binge drinking is the most common, costly, and deadly pattern of excessive alcohol use. Addressing this major public health problem requires a better understanding of the underlying neurobiology of binge drinking. One region of particular interest for binge-drinking is the prelimbic cortex (PL). We have previously shown that excitatory and inhibitory signaling in the PL is altered following a variety of models of ethanol exposure. In addition, our preliminary data indicates that somatostatin neurons in the PL are involved in alcohol binge drinking in both sexes. This is particularly novel as it represents a promising neuronal population capable of reducing binge drinking behavior. Our project will (1) investigate how PL somatostatin neurons interact with other neurons (synaptic connectivity and signaling), and (2) what role they play in binge drinking (chemogenetic activation and inhibition). Taken together, these experiments will assess the hypothesis that somatostatin neurons in the PL are a promising therapeutic target for alcohol use disorder, and binge drinking in particular.