This paper by Hongping Xu, Moran Furman, Yann S. Mineur, Hui Chen, Sarah L. King, David Zenisek, Z. Jimmy Zhou, Daniel A. Butts, Ning Tian, Marina R. Picciotto and Michael Crair describes a collaborative effort from several laboratories from Yale University, the University of Maryland and the University of Utah. Two former postdoctoral fellows from the laboratory of Ning Tian, Drs. Hongping Xu (the first author) and Hui Chen, were principal contributors. The results described in this paper 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 and, therefore, suggests that specific patterns of spontaneous activity throughout the developing brain are essential in the emergence of specific and distinct patterns of neuronal connectivity. What does this mean? It gets to one of the fundamental issues of nature vs. nurture in that the genes are thought to establish the fundamental pattern for connectivity in neuronal systems and are then fine tuned or refined during development. This paper therefore examines the influence of experience on neuronal connectivity of the visual system and concludes that the intrinsic “experience” of internally generated neural activity in the neural retina is responsible for formation of proper circuitry.