Shah Ruchir D, Crair Michael C
Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Neurosci. 2008 Jan 2;28(1):292-303. doi: 10.1523/JNEUROSCI.4276-07.2008.
During development, spontaneous retinal waves are thought to provide an instructive signal for retinotopic map formation in the superior colliculus. In mice lacking the beta2 subunit of nicotinic ACh receptors (beta2-/-), 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 beta2-/- 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 beta2-/- 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.
在发育过程中，自发视网膜波被认为为上丘中视网膜拓扑图的形成提供了一种指导性信号。在缺乏烟碱型乙酰胆碱受体β2亚基（β2-/-）的小鼠中，出生后第一周没有相关的视网膜波，但在出生后第二周恢复。在对照视网膜-上丘突触中，体外分析显示，出生后第一周AMPA/NMDA比值和AMPA量子幅度增加，而沉默突触的发生率降低。然而，在年龄匹配的β2-/-小鼠中，在没有视网膜波的情况下，这些参数在出生后第一周保持不变，但在第二周结束时迅速成熟到对照水平，这表明相关波的延迟出现能够驱动突触成熟。为了研究是否存在这样的机制关系，我们应用了一种“基于爆发”的可塑性方案，该方案模拟了视网膜波期间的同步活动。我们发现，这种激活模式确实能够在出生后第一周早期（出生后第3天（P3）至P4）平均在各基因型中诱导突触增强[长时程增强（LTP）]，有趣的是，在第一周结束时（P6-P7），未成熟的β2-/-突触中的LTP能力明显大于成熟的对照突触。总之，我们的结果表明，视网膜波通过一种与自然波统计生理相关的学习规则驱动视网膜-上丘突触成熟，并且这些突触变化可能在视网膜拓扑图细化过程中起指导作用。
