Retinal waves are disrupted and infrequent in vivo in β2-nAChR−/− (β2-KO) mice
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Retinal waves are dissociated from postsynaptic midbrain activity in β2-KO mice
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Retinal deletion of β2-nAChR abolishes waves and disrupts visual circuit refinement
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Rescue of wave frequency restores eye-specific segregation, but not retinotopy
Summary
The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial, largely due to the inherent difficulty recording neural activity in early development. Here, we describe genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a decoupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience.
