Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 1, Pages 292-303Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4276-07.2008
Keywords
retinal waves; superior colliculus; activity dependent; synapse development; mouse; map refinement
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Funding
- NEI NIH HHS [T32 EY007001, T32 EY07001, P30 EY000785, R01 EY015788] Funding Source: Medline
- NIMH NIH HHS [R01 MH062639] Funding Source: Medline
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During development, spontaneous retinal waves are thought to provide an instructive signal for retinotopic map formation in the superior colliculus. In mice lacking the beta 2 subunit of nicotinic ACh receptors (beta 2(-/-)), correlated retinal waves are absent during the first postnatal week, but return during the second postnatal week. In control retinocollicular synapses, in vitro analysis reveals that AMPA/NMDA ratios and AMPA quantal amplitudes increase during the first postnatal week while the prevalence of silent synapses decreases. In age-matched beta 2(-/-) mice, however, these parameters remain unchanged through the first postnatal week in the absence of retinal waves, but quickly mature to control levels by the end of the second week, suggesting that the delayed onset of correlated waves is able to drive synapse maturation. To examine whether such a mechanistic relationship exists, we applied a burst-based plasticity protocol that mimics coincident activity during retinal waves. We find that this pattern of activation is indeed capable of inducing synaptic strengthening [long-term potentiation (LTP)] on average across genotypes early in the first postnatal week [postnatal day 3 (P3) to P4] and, interestingly, that the capacity for LTP at the end of the first week (P6-P7) is significantly greater in immature beta 2(-/-) synapses than in mature control synapses. Together, our results suggest that retinal waves drive retinocollicular synapse maturation through a learning rule that is physiologically relevant to natural wave statistics and that these synaptic changes may serve an instructive role during retinotopic map refinement.
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