期刊
JOURNAL OF NEUROSCIENCE
卷 32, 期 16, 页码 5426-5439出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0194-12.2012
关键词
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资金
- Hope for Vision Foundation
- Edward Mallinckrodt Jr. Foundation
- Alfred P. Sloan Foundation
- Whitehall Foundation
- National Institutes of Health [R01 EY021855, K12 EY016336, P30 EY0268]
- Research to Prevent Blindness unrestricted grant
Spontaneous activity is thought to regulate synaptogenesis in many parts of the developing nervous system. In vivo evidence for this regulation, however, is scarce and comes almost exclusively from experiments in which normal activity was reduced or blocked completely. Thus, whether spontaneous activity itself promotes synaptogenesis or plays a purely permissive role remains uncertain. In addition, how activity influences synapse dynamics to shape connectivity and whether its effects among neurons are uniform or cell-type-dependent is unclear. In mice lacking the cone-rod homeobox gene (Crx), photoreceptors fail to establish normal connections with bipolar cells (BCs). Here, we find that retinal ganglion cells (RGCs) in Crx(-/-) mice become rhythmically hyperactive around the time of eye opening as a result of increased spontaneous glutamate release from BCs. This elevated neurotransmission enhances synaptogenesis between BCs and RGCs, without altering the overall circuit architecture. Using live imaging, we discover that spontaneous activity selectively regulates the rate of synapse formation, not elimination, in this circuit. Reconstructions of the connectivity patterns of three BC types with a shared RGC target further revealed that neurotransmission specifically promotes the formation of multisynaptic appositions from one BC type without affecting the maintenance or elimination of connections from the other two. Although hyperactivity in Crx(-/-) mice persists, synapse numbers do not increase beyond 4 weeks of age, suggesting closure of a critical period for synaptic refinement in the inner retina. Interestingly, despite their hyperactivity, RGC axons maintain normal eye-specific territories and cell-type-specific layers in the dorsal lateral geniculate nucleus.
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