Institute of Neuroscience, Newcastle University Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
J Physiol. 2014 Apr 1;592(7):1545-63. doi: 10.1113/jphysiol.2013.262840. Epub 2013 Dec 23.
The immature retina generates spontaneous waves of spiking activity that sweep across the ganglion cell layer during a limited period of development before the onset of visual experience. The spatiotemporal patterns encoded in the waves are believed to be instructive for the wiring of functional connections throughout the visual system. However, the ontogeny of retinal waves is still poorly documented as a result of the relatively low resolution of conventional recording techniques. Here, we characterize the spatiotemporal features of mouse retinal waves from birth until eye opening in unprecedented detail using a large-scale, dense, 4096-channel multielectrode array that allowed us to record from the entire neonatal retina at near cellular resolution. We found that early cholinergic waves propagate with random trajectories over large areas with low ganglion cell recruitment. They become slower, smaller and denser when GABAA signalling matures, as occurs beyond postnatal day (P) 7. Glutamatergic influences dominate from P10, coinciding with profound changes in activity dynamics. At this time, waves cease to be random and begin to show repetitive trajectories confined to a few localized hotspots. These hotspots gradually tile the retina with time, and disappear after eye opening. Our observations demonstrate that retinal waves undergo major spatiotemporal changes during ontogeny. Our results support the hypotheses that cholinergic waves guide the refinement of retinal targets and that glutamatergic waves may also support the wiring of retinal receptive fields.
不成熟的视网膜在视觉经验开始之前的有限发育时期会产生自发的尖峰活动波，这些波在节细胞层中传播。人们认为，这些波中编码的时空模式对整个视觉系统中功能连接的布线具有指导意义。然而，由于传统记录技术的分辨率相对较低，视网膜波的个体发生仍然记录不足。在这里，我们使用大规模的、密集的 4096 通道多电极阵列，以前所未有的细节描述了从出生到睁眼期间小鼠视网膜波的时空特征，该阵列允许我们以近细胞分辨率记录整个新生鼠的视网膜。我们发现，早期的胆碱能波在大区域内以随机轨迹传播，招募的节细胞较少。当 GABA 能信号成熟时，即出生后第 7 天以后，它们会变得更慢、更小、更密集。谷氨酸能的影响从 P10 开始占主导地位，此时活动动力学发生深刻变化。此时，波不再是随机的，开始表现出局限于少数几个局部热点的重复轨迹。随着时间的推移，这些热点逐渐覆盖整个视网膜，在睁眼后消失。我们的观察表明，视网膜波在个体发生过程中经历了主要的时空变化。我们的结果支持以下假说：胆碱能波指导视网膜靶标的细化，而谷氨酸能波也可能支持视网膜感受野的布线。
