Vierkant Valerie, Xie Xueyi, Huang Zhenbo, He Lian, Bancroft Eric, Wang Xuehua, Nguyen Tran, Srinivasan Rahul, Zhou Yubin, Wang Jun
Department of Neuroscience and Experimental Therapeutics, School of Medicine, Texas A&M University Health Science Center, Bryan, Texas, USA.
Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, Texas, USA.
Alcohol Clin Exp Res (Hoboken). 2024 Sep;48(9):1728-1739. doi: 10.1111/acer.15412. Epub 2024 Aug 2.
Alcohol use disorder (AUD) is a complex condition, and it remains unclear which specific neuronal substrates mediate alcohol-seeking and -taking behaviors. Engram cells and their related ensembles, which encode learning and memory, may play a role in this process. We aimed to assess the precise neural substrates underlying alcohol-seeking and -taking behaviors and determine how they may affect one another.
Using FLiCRE (Fast Light and Calcium-Regulated Expression; a newly developed technique which permits the trapping of acutely activated neuronal ensembles) and operant self-administration (OSA), we tagged striatal neurons activated during alcohol-taking behaviors. We used FLiCRE to express an inhibitory halorhodopsin in alcohol-taking neurons, permitting loss-of-function manipulations.
We found that the inhibition of OSA-tagged alcohol-taking neurons decreased both alcohol-seeking and -taking behaviors in future OSA trials. In addition, optogenetic inhibition of these OSA-tagged alcohol-taking neurons during extinction training facilitated the extinction of alcohol-seeking behaviors. Furthermore, inhibition of these OSA-tagged alcohol-taking neurons suppressed the reinstatement of alcohol-seeking behaviors, but, interestingly, it did not significantly suppress alcohol-taking behaviors during reinstatement.
Our findings suggest that alcohol-taking neurons are crucial for future alcohol-seeking behaviors during extinction and reinstatement. These results may help in the development of new therapeutic approaches to enhance extinction and suppress relapse in individuals with AUD.
酒精使用障碍（AUD）是一种复杂的病症，目前尚不清楚哪些特定的神经元底物介导了觅酒和饮酒行为。编码学习和记忆的记忆印迹细胞及其相关神经元集群可能在此过程中发挥作用。我们旨在评估觅酒和饮酒行为背后精确的神经底物，并确定它们之间可能如何相互影响。
使用FLiCRE（快速光和钙调节表达；一种新开发的技术，可捕获急性激活的神经元集群）和操作性自我给药（OSA），我们标记了在饮酒行为期间被激活的纹状体神经元。我们使用FLiCRE在饮酒神经元中表达一种抑制性嗜盐视紫红质，以进行功能丧失操作。
我们发现，抑制经OSA标记的饮酒神经元会降低未来OSA试验中的觅酒和饮酒行为。此外，在消退训练期间对这些经OSA标记的饮酒神经元进行光遗传学抑制促进了觅酒行为的消退。此外，抑制这些经OSA标记的饮酒神经元可抑制觅酒行为的恢复，但有趣的是，它在恢复期间并未显著抑制饮酒行为。
我们的研究结果表明，饮酒神经元对于消退和恢复期间未来的觅酒行为至关重要。这些结果可能有助于开发新的治疗方法，以增强酒精使用障碍个体的消退能力并抑制复发。
