Augustine Farhan, Doss Shawn M, Pellicciotti Justin, Mahate Sahar, Singer Harvey S
Johns Hopkins University School of Medicine, Department of Neurology, and the Kennedy Krieger Institute, Baltimore, MD, USA; University of Maryland Baltimore County, Department of Biological Sciences, Baltimore, MD, USA.
Johns Hopkins University, Baltimore, MD, USA.
Neuroscience. 2025 Mar 5;568:324-332. doi: 10.1016/j.neuroscience.2025.01.005. Epub 2025 Jan 3.
Repetitive motor behaviors are common in both neurotypical and developmentally delayed populations. The neural mechanisms underlying these behaviors are not fully understood, but cortical-basal ganglia-thalamo-cortical (CBGTC) circuitry is often implicated. Peromyscus maniculatus bairdii (deer mice), which exhibit spontaneous repetitive actions analogous to human motor stereotypies and obsessive-compulsive behaviors, serve as an effective model for studying repetitive behaviors. This preliminary study investigates the relationship between repetitive motor activity and striatal expression of endogenous opioids and dopamine receptors in deer mice. Behavioral assessment involved video-confirmed quantification of leaping, hopping, and rearing in seven mice. Using in-situ mRNA hybridization (RNAscope®), we quantified mRNA levels of proenkephalin, prodynorphin, mu, delta, and kappa opioid receptors, and D1 and D2 dopamine receptors in four striatal sub-regions: dorsomedial (DMS), dorsolateral (DLS), ventromedial (VMS), and ventrolateral (VLS). Associations between mRNA fluorescence and behavioral activity were evaluated using Spearman's rank correlations adjusted for false discovery rate (FDR). Results showed a significant positive correlation between D2 dopamine receptor (DRD2) mRNA expression in the DLS and total repetitive activity (p < 0.001). Additional positive DRD2 correlations in other regions did not reach significance after FDR adjustment. No significant relationships were found for DRD1 or endogenous opioid markers. These findings suggest that DRD2 expression in the DLS may modulate repetitive behaviors in deer mice, highlighting the role of dopaminergic pathways within CBGTC circuitry. However, limitations such as small sample size and lack of protein-level verification require further investigation. Future research should explore translational implications of DRD2 modulation and analyze additional brain regions.
重复性运动行为在神经发育正常和发育迟缓的人群中都很常见。这些行为背后的神经机制尚未完全了解，但皮质-基底神经节-丘脑-皮质（CBGTC）回路常被认为与之相关。白足鼠（鹿鼠）表现出类似于人类运动刻板行为和强迫症行为的自发重复性动作，是研究重复性行为的有效模型。这项初步研究调查了鹿鼠重复性运动活动与纹状体内源性阿片类物质和多巴胺受体表达之间的关系。行为评估包括通过视频确认对7只小鼠的跳跃、单脚跳和直立行为进行量化。我们使用原位mRNA杂交技术（RNAscope®），对四个纹状体亚区域：背内侧（DMS）、背外侧（DLS）、腹内侧（VMS）和腹外侧（VLS）中脑啡肽原、强啡肽原、μ、δ和κ阿片受体以及D1和D2多巴胺受体的mRNA水平进行了量化。使用针对错误发现率（FDR）调整的Spearman等级相关性评估mRNA荧光与行为活动之间的关联。结果显示，DLS中D2多巴胺受体（DRD2）mRNA表达与总重复性活动之间存在显著正相关（p < 0.001）。在FDR调整后，其他区域中DRD2的额外正相关未达到显著水平。未发现DRD1或内源性阿片类物质标记物有显著关系。这些发现表明，DLS中DRD2的表达可能调节鹿鼠的重复性行为，突出了CBGTC回路中多巴胺能通路的作用。然而，样本量小和缺乏蛋白质水平验证等局限性需要进一步研究。未来的研究应探索DRD2调节的转化意义，并分析其他脑区。
