Prelimbic somatostatin peptide signaling in binge ethanol consumption

项目摘要 酒精使用障碍(AUD)是一种复杂的精神障碍，具有巨大的社会和个人压力，涉及 许多大脑区域和细胞类型。很少有有效的治疗方法专门针对预防酗酒 喝酒。了解酗酒的潜在神经生物学对于预防和治疗至关重要 这一重大的公共卫生问题。我们实验室正在进行的工作试图了解生长抑素(SST)是如何 GABA能神经元在前交叉(PL)皮质的表达，长期以来一直被认为与其他 神经精神障碍作为一种抗抑郁、增强韧性的多肽能神经元群体，可能 作为AUD的治疗靶点。这项提案的首要目标是了解如何 SST肽信号对PL回路功能的贡献，以及这些通路是如何 受酗酒的影响。使用电生理学、电路标测、 纤维光度学，和行为，我们将探索三个互补但不重叠的目标：我们将 演示SST如何调制初级锥体神经元，SST调制的特定输出，以及 SST作用于PL皮质的整体行为表型。我们将在以下时间进行这些实验 控制条件和在酗酒的背景下。 综上所述，这些实验将确定SST多肽对特定途径的整体作用 前额叶皮质的环路。此外，我们还将建立SST肽在体内对酒精消费的影响 和焦虑样行为，提供了PL中SST的全面机制和功能特征 大脑皮层。这些结果将建立在我们之前发现的基础上，以阐明SST肽的确切作用。 重要的是，我们希望这些结果有可能为澳门氏症的新治疗目标提供信息。

Project Summary Alcohol Use Disorder (AUD) is a complex psychiatric disorder with large societal and personal strain, involving many brain regions and cell types. Few effective treatments exist that specifically target the prevention of binge drinking. Understanding the underlying neurobiology of binge drinking is essential for preventing and treating this major public health problem. Ongoing work in our lab seeks to understand how somatostatin (SST) expressing GABAergic neurons in the prelimbic (PL) cortex, which have long been implicated in other neuropsychiatric disorders as an anti-depressive, resilience-conferring population of peptidergic neurons, may function as a therapeutic target for AUD. The overarching goal of this proposal is to understand how SST peptide signaling contributes to PL circuitry function, and how these pathways are modulated by binge alcohol consumption. Using a combination of electrophysiology, circuit mapping, fiber photometry, and behavior, we will explore three complementary but non-overlapping aims: we will demonstrate how SST modulates prelimbic pyramidal neurons, the specific outputs modulated by SST, and the overall behavioral phenotype of SST administration to the PL cortex. We will conduct these experiments during control conditions and in the context of binge drinking. Taken together, these experiments will determine the overall role of SST peptide effects on pathway-specific circuits of the PL cortex. In addition, we will establish the in vivo effects of SST peptide on alcohol consumption and anxiety-like behaviors, providing an overall mechanistic and functional characterization of SST in the PL cortex. These results will build upon our previous findings to elucidate the precise role of the SST peptide. Importantly, we expect these results to have the potential to inform new treatment targets for AUD.