Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Neuron. 2011 Jun 23;70(6):1115-27. doi: 10.1016/j.neuron.2011.04.028.
Complex neural circuits in the mammalian brain develop through a combination of genetic instruction and activity-dependent refinement. The relative role of these factors and the form of neuronal activity responsible for circuit development is a matter of significant debate. In the mammalian visual system, retinal ganglion cell projections to the brain are mapped with respect to retinotopic location and eye of origin. We manipulated the pattern of spontaneous retinal waves present during development without changing overall activity levels through the transgenic expression of β2-nicotinic acetylcholine receptors in retinal ganglion cells of mice. We used this manipulation to demonstrate that spontaneous retinal activity is not just permissive, but instructive in the emergence of eye-specific segregation and retinotopic refinement in the mouse visual system. This suggests that specific patterns of spontaneous activity throughout the developing brain are essential in the emergence of specific and distinct patterns of neuronal connectivity.
哺乳动物大脑中的复杂神经网络通过遗传指令和活动依赖性的修正共同发育。这些因素的相对作用以及负责回路发育的神经元活动的形式是一个备受争议的问题。在哺乳动物的视觉系统中，视网膜神经节细胞向大脑的投射与视网膜位置和眼起源有关。我们通过在小鼠的视网膜神经节细胞中过表达β2-烟碱型乙酰胆碱受体，在不改变整体活动水平的情况下，操纵发育过程中出现的自发性视网膜波的模式。我们利用这种操作，证明了自发性视网膜活动不仅是允许的，而且在小鼠视觉系统中眼特异性分离和视网膜拓扑细化的出现中具有指导作用。这表明，在整个发育中的大脑中出现的特定模式的自发性活动对于特定和独特的神经元连接模式的出现是必不可少的。
