Abstract
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 invivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week inPCs and, to a lesserextent, 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.
Highlights
The results to be presented indicate that desynchronization of climbing fiber (CF) responses during the first postnatal week is a crucial step for the maturation of Purkinje cell (PC) population activity
The activation of the CF-PC synapse generates a burst of action potentials known as a complex spike (CS) (Eccles et al, 1966), which triggers a widespread influx of calcium into PCs (Miyakawa et al, 1992)
Electrotonic coupling through gap junctions between olivary neurons synchronizes spontaneous CSs in Developmental Desynchronization of Population Activity of PCs We bulk loaded the fluorescent calcium indicator Oregon green 488 BAPTA-1 AM (OGB-1) into the cerebellar cortex of young C57BL/6 mice and monitored spontaneous activity in PCs using in vivo two-photon calcium imaging
Summary
The climbing fiber to Purkinje cell network is extensively remodeled during postnatal development. Good et al show that in vivo population activity of Purkinje cells in response to climbing fiber synaptic inputs is highly synchronized in newborn mice and massively desynchronized due to climbing fiber network refinement. Highlights d Purkinje cell (PC) population activity was examined in developing cerebellum in vivo d Climbing fiber (CF) responses are highly synchronized in PCs of early postnatal mice d CF responses are desynchronized and reach adult level in the first postnatal week d CF network refinement is a structural basis for desynchronization of CF responses. 2017, Cell Reports 21, 2066–2073 November 21, 2017 a 2017 The Author(s).
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