Some aspects of the retinal wave activity, such as coincidences of RGC activity over second-long time scales, specifically contain information that could instruct synaptic refinement. These retinal waves have distinct spatiotemporal properties that have been studied in detail through a variety of multi-electrode and calcium imaging studies. This activity consists of correlated bursts of action potentials that spread across large regions of the retinal ganglion cell layer. This synaptic refinement-as well as similar refinement in the developing visual cortex and superior colliculus -is known to require spontaneously generated activity in the developing retina. At the system level, this synaptic refinement results in segregation into eye-specific regions and establishment of fine retinotopy, with neighboring RGCs projecting to neighboring LGN neurons. At the earliest ages studied, LGN neurons receive inputs from a large number of RGCs from both eyes, and this number reduces to one or a few over the course of development. The synaptic refinement of retinal ganglion cell (RGC) axons in the developing lateral geniculate nucleus (LGN) during early postnatal development in rodents provides an opportunity to study synaptic plasticity in this larger context, since the activity over the inputs to the LGN and the resulting developmental outcome are both well characterized. Though synaptic plasticity is a feature of most excitatory synapses in the brain, how it functions in realistic contexts is largely unclear because its effects usually only manifest on the system level. We then demonstrate how this learning rule is matched to properties of the retinal waves in order to robustly drive the synaptic refinement that occurs in the visual system. By replaying the retinal wave activity as it appears at single LGN synapses, we observe a novel learning rule that describes a relatively simple computation for the developing synapse in the context of retinal wave activity. Here, we study connections in the visual pathway between the retina and lateral geniculate nucleus (LGN), which-to develop correctly-require spontaneous “retinal waves” before the eye is responsive to light. Throughout life, such activity-dependent synaptic changes are likely driven by experience and are thought to underlie learning and memory, but during early stages of development, they are often driven by activity spontaneously generated within the brain. One common strategy uses neural activity itself as feedback to instruct individual connections (synapses) through synaptic learning rules that delineate which patterns of activity strengthen the synapse and which weaken it. The brain is comprised of an immense number of connections between neurons, and clever strategies are required to achieve the correct wiring during development.
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