Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan; Department of Neurophysiology, Faculty of Medicine, University of Yamanashi, Yamanashi 409-3898, Japan.
Cell Rep. 2017 Nov 21;21(8):2066-2073. doi: 10.1016/j.celrep.2017.10.101.
Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the climbing fiber (CF) to Purkinje cell (PC) network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity.
神经回路在出生后发育过程中经历大规模的精细化。在发育中的小脑,通过消除早期形成的冗余的 climbing fiber (CF) 到 Purkinje cell (PC) 突触,CF 到 PC 的网络被剧烈重塑。为了研究 CF 网络精细化对出生后发育过程中 PC 群体活动的影响,我们使用在体双光子钙成像来监测邻近 PC 中的自发 CF 反应和附近 CF 末梢的群体活动。在新生小鼠中,群体活动高度同步,并且在 PC 中和在较小程度上在 CF 末梢中的同步程度在出生后的第一周逐渐下降。缺乏 P/Q 型电压门控钙通道或谷氨酸受体 δ2 的敲除小鼠,其中 CF 网络的精细化严重受损,表现出 PC 群体活动中异常高的同步水平。这些结果表明,CF 网络的精细化是 PC 群体活动发育去同步和成熟的结构基础。