IntroductionOverreliance on habit is linked with disorders, such as drug addiction and obsessive-compulsive disorder, and there is increasing interest in the use of repetitive transcranial magnetic stimulation (rTMS) to alter neuronal activity in the relevant pathways and for therapeutic outcomes. In this study, we researched the brains of ephrin-A2A5−/− mice, which previously showed perseverative behavior in progressive-ratio tasks, associated with low cellular activity in the nucleus accumbens. We investigated whether rTMS treatment had altered the activity of the dorsal striatum in a way that suggested altered hierarchical recruitment of brain regions from the ventral striatum to the dorsal striatum, which is linked to abnormal habit formation.MethodsBrain sections from a limited number of mice that underwent training and performance on a progressive ratio task with and without low-intensity rTMS (LI-rTMS) were taken from a previous study. We took advantage of the previous characterization of perseverative behavior to investigate the contribution of different neuronal subtypes and striatal regions within this limited sample. Striatal regions were stained for c-Fos as a correlate of neuronal activation for DARPP32 to identify medium spiny neurons (MSNs) and for GAD67 to identify GABA-ergic interneurons.Results and discussionContrary to our hypothesis, we found that neuronal activity in ephrin-A2A5−/− mice still reflected the typical organization of goal-directed behavior. There was a significant difference in the proportion of neuronal activity across the striatum between experimental groups and control but no significant effects identifying a specific regional change. However, there was a significant group by treatment interaction which suggests that MSN activity is altered in the dorsomedial striatum and a trend suggesting that rTMS increases ephrin-A2A5−/− MSN activity in the DMS. Although preliminary and inconclusive, the analysis of this archival data suggests that investigating circuit-based changes in striatal regions may provide insight into chronic rTMS mechanisms that could be relevant to treating disorders associated with perseverative behavior.

中文翻译：

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持久性肝配蛋白-A2A5−/− 小鼠的背侧纹状体 c-Fos 活性以及低强度 rTMS 的细胞效应

简介过度依赖习惯与药物成瘾和强迫症等疾病有关，人们越来越关注使用重复经颅磁刺激 (rTMS) 来改变相关通路中的神经元活动并获得治疗结果。在这项研究中，我们研究了 ephrin-A2A5 的大脑−/−小鼠之前在渐进比例任务中表现出持久的行为，这与伏隔核中的低细胞活动有关。我们研究了 rTMS 治疗是否改变了背侧纹状体的活动，从而表明从腹侧纹状体到背侧纹状体的大脑区域的分层募集发生了改变，这与异常习惯的形成有关。接受或不使用低强度 rTMS (LI-rTMS) 的渐进比率任务的训练和表现取自之前的研究。我们利用之前对持续行为的描述来研究这个有限样本中不同神经元亚型和纹状体区域的贡献。−/−老鼠仍然反映了目标导向行为的典型组织。实验组和对照组之间纹状体神经元活动的比例存在显着差异，但没有识别特定区域变化的显着影响。然而，有一个显着的治疗相互作用组表明背内侧纹状体中的 MSN 活性发生了改变，并且趋势表明 rTMS 增加了 ephrin-A2A5−/−DMS 中的 MSN 活动。尽管是初步的和不确定的，但对这些档案数据的分析表明，研究纹状体区域基于回路的变化可能会提供对慢性 rTMS 机制的深入了解，这些机制可能与治疗与持续行为相关的疾病有关。