Thiry Louise, Lemieux Maxime, D Laflamme Olivier, Bretzner Frédéric
Centre de Recherche du Centre Hospitalier, (CHU) de Québec-CHUL and Département de Psychiatrie et Neurosciences de l'Université Laval, Québec, Québec, Canada.
Centre de Recherche du Centre Hospitalier, (CHU) de Québec-CHUL and Département de Psychiatrie et Neurosciences de l'Université Laval, Québec, Québec, Canada
J Neurophysiol. 2016 Mar;115(3):1338-54. doi: 10.1152/jn.00557.2015. Epub 2015 Dec 9.
Locomotion is controlled by spinal circuits that generate rhythm and coordinate left-right and flexor-extensor motoneuronal activities. The outputs of motoneurons and spinal interneuronal circuits are shaped by sensory feedback, relaying peripheral signals that are critical to the locomotor and postural control. Several studies in invertebrates and vertebrates have argued that the Down syndrome cell adhesion molecule (DSCAM) would play an important role in the normal development of neural circuits through cell spacing and targeting, axonal and dendritic branching, and synapse establishment and maintenance. Although there is evidence that DSCAM is important for the normal development of neural circuits, little is known about its functional contribution to spinal motor circuits. We show here that adult DSCAM(2J) mutant mice, lacking DSCAM, exhibit a higher variability in their locomotor pattern and rhythm during treadmill locomotion. Retrograde tracing studies in neonatal isolated spinal cords show an increased number of spinal commissural interneurons, which likely contributes to reducing the left-right alternation and to increasing the flexor/swing duration during neonatal and adult locomotion. Moreover, our results argue that, by reducing the peripheral excitatory drive onto spinal motoneurons, the DSCAM mutation reduces or abolishes spinal reflexes in both neonatal isolated spinal cords and adult mice, thus likely impairing sensorimotor control. Collectively, our functional, electrophysiological, and anatomical studies suggest that the mammalian DSCAM protein is involved in the normal development of spinal locomotor and sensorimotor circuits.
运动由脊髓回路控制，这些回路产生节律并协调左右以及屈肌 - 伸肌运动神经元的活动。运动神经元和脊髓中间神经元回路的输出受到感觉反馈的影响，传递对运动和姿势控制至关重要的外周信号。对无脊椎动物和脊椎动物的多项研究表明，唐氏综合征细胞粘附分子（DSCAM）通过细胞间距和靶向、轴突和树突分支以及突触的建立和维持，在神经回路的正常发育中发挥重要作用。尽管有证据表明DSCAM对神经回路的正常发育很重要，但关于其对脊髓运动回路的功能贡献却知之甚少。我们在此表明，缺乏DSCAM的成年DSCAM(2J)突变小鼠在跑步机运动期间的运动模式和节律具有更高的变异性。对新生离体脊髓进行的逆行追踪研究表明，脊髓连合中间神经元的数量增加，这可能导致在新生和成年运动期间左右交替减少以及屈肌/摆动持续时间增加。此外，我们的结果表明，通过减少脊髓运动神经元的外周兴奋性驱动，DSCAM突变会减少或消除新生离体脊髓和成年小鼠中的脊髓反射，从而可能损害感觉运动控制。总体而言，我们的功能、电生理和解剖学研究表明，哺乳动物DSCAM蛋白参与脊髓运动和感觉运动回路的正常发育。
