Lousada Eliana, Boudreau Mathieu, Cohen-Adad Julien, Nait Oumesmar Brahim, Burguière Eric, Schreiweis Christiane
Team 'Neurophysiology of Repetitive Behaviours' (NERB), Institut du Cerveau, Inserm U1127, Centre National de la Recherche Scientifique (CNRS) U7225, Sorbonne Universités, Hôpital de la Pitié-Salpêtrière, 75013 Paris, France.
Montreal Heart Institute, Montréal, QC H1T 1C8, Canada.
Brain Sci. 2021 Oct 14;11(10):1353. doi: 10.3390/brainsci11101353.
Pathological repetitive behaviours are a common feature of various neuropsychiatric disorders, including compulsions in obsessive-compulsive disorder or tics in Gilles de la Tourette syndrome. Clinical research suggests that compulsive-like symptoms are related to associative cortico-striatal dysfunctions, and tic-like symptoms to sensorimotor cortico-striatal dysfunctions. The knockout mouse (-KO), the current reference model to study such repetitive behaviours, presents both associative as well as sensorimotor cortico-striatal dysfunctions. Previous findings point to deficits in both macro-, as well as micro-circuitry, both of which can be affected by neuronal structural changes. However, to date, structural connectivity has not been analysed. Hence, in the present study, we conducted a comprehensive structural characterisation of both associative and sensorimotor striatum as well as major cortical areas connecting onto these regions. Besides a thorough immunofluorescence study on oligodendrocytes, we applied AxonDeepSeg, an open source software, to automatically segment and characterise myelin thickness and axon area. We found that axon calibre, the main contributor to changes in conduction speed, is specifically reduced in the associative striatum of the -KO mouse; myelination per se seems unaffected in associative and sensorimotor cortico-striatal circuits.
病理性重复行为是多种神经精神疾病的常见特征,包括强迫症中的强迫行为或抽动秽语综合征中的抽动症状。临床研究表明,强迫样症状与联合皮质-纹状体功能障碍有关,抽动样症状与感觉运动皮质-纹状体功能障碍有关。基因敲除小鼠(-KO)是目前研究此类重复行为的参考模型,它同时存在联合及感觉运动皮质-纹状体功能障碍。先前的研究结果指出,其在宏观和微观回路方面均存在缺陷,二者均可受神经元结构变化的影响。然而,迄今为止,尚未对结构连接性进行分析。因此,在本研究中,我们对联合纹状体和感觉运动纹状体以及连接到这些区域的主要皮质区域进行了全面的结构表征。除了对少突胶质细胞进行深入的免疫荧光研究外,我们还应用了开源软件AxonDeepSeg来自动分割并表征髓鞘厚度和轴突面积。我们发现,轴突直径是传导速度变化的主要影响因素,在基因敲除小鼠的联合纹状体中特异性降低;联合和感觉运动皮质-纹状体回路中的髓鞘形成本身似乎未受影响。