Sokoloff Greta, Uitermarkt Brandt D, Blumberg Mark S
Department of Psychology, University of Iowa, Iowa City, Iowa.
Delta Center, The University of Iowa, Iowa City, Iowa.
Dev Neurobiol. 2015 Oct;75(10):1140-53. doi: 10.1002/dneu.22177. Epub 2014 Apr 25.
The cerebellum is critical for sensorimotor integration and undergoes extensive postnatal development. During the first postnatal week in rats, climbing fibers polyinnervate Purkinje cells and, before granule cell migration, mossy fibers make transient, direct connections with Purkinje cells. Activity-dependent processes are assumed to play a critical role in the development and refinement of these and other aspects of cerebellar circuitry. However, the sources and patterning of activity have not been described. We hypothesize that sensory feedback (i.e., reafference) from myoclonic twitches in sleeping newborn rats is a prominent driver of activity for the developing cerebellum. Here, in 6-day-old rats, we show that Purkinje cells exhibit substantial state-dependent changes in complex and simple spike activity-primarily during active sleep. In addition, this activity increases significantly during bouts of twitching. Moreover, the surprising observation of twitch-dependent increases in simple spike activity at this age suggests a functional engagement of mossy fibers before the parallel fiber system has developed. Based on these and other results, we propose that twitching comprises a unique class of self-produced movement that drives critical aspects of activity-dependent development in the cerebellum and other sensorimotor systems.
小脑对于感觉运动整合至关重要,且在出生后经历广泛发育。在大鼠出生后的第一周,攀缘纤维多神经支配浦肯野细胞,并且在颗粒细胞迁移之前,苔藓纤维与浦肯野细胞形成短暂的直接连接。依赖活动的过程被认为在小脑回路的这些及其他方面的发育和精细化中起关键作用。然而,活动的来源和模式尚未得到描述。我们假设,睡眠新生大鼠肌阵挛抽搐的感觉反馈(即再传入)是发育中小脑活动的一个重要驱动因素。在此,我们在6日龄大鼠中发现,浦肯野细胞在复杂和简单锋电位活动中表现出显著的状态依赖性变化——主要在主动睡眠期间。此外,这种活动在抽搐发作期间显著增加。而且,在这个年龄段观察到简单锋电位活动依赖于抽搐增加,这一惊人发现表明在平行纤维系统发育之前苔藓纤维就已发挥功能作用。基于这些及其他结果,我们提出抽搐构成一类独特的自我产生的运动,它驱动小脑和其他感觉运动系统中依赖活动发育的关键方面。