Abstract

Granule cells (GCs) in the cerebellar cortex are important for sparse encoding of afferent sensorimotor information. Modeling studies show that GCs can perform their function most effectively when they have four dendrites. Indeed, mature GCs have four short dendrites on average, each terminating in a claw-like ending that receives both excitatory and inhibitory inputs. Immature GCs, however, have significantly more dendrites—all without claws. How these redundant dendrites are refined during development is largely unclear. Here, we used in vivo time-lapse imaging and immunohistochemistry to study developmental refinement of GC dendritic arbors and its relation to synapse formation. We found that while the formation of dendritic claws stabilized the dendrites, the selection of surviving dendrites was made before claw formation, and longer immature dendrites had a significantly higher chance of survival than shorter dendrites. Using immunohistochemistry, we show that glutamatergic and GABAergic synapses are transiently formed on immature GC dendrites, and the number of GABAergic, but not glutamatergic, synapses correlates with the length of immature dendrites. Together, these results suggest a potential role of transient GABAergic synapses on dendritic selection and show that preselected dendrites are stabilized by the formation of dendritic claws—the site of mature synapses.

Highlights

  • The specific pattern of a neuronal dendritic arbor determines how that neuron integrates synaptic inputs from multiple, diverse presynaptic cells[1,2,3]

  • Some granule cells (GCs) receive excitatory inputs from unipolar brush cells, the density of unipolar brush cells is low in lobules 6–7; GCs imaged in this study receive excitatory inputs predominantly from mossy fiber (MF)

  • A total of 21 developing GCs were imaged from 6 pups, out of which 7 cells were imaged from P11 onwards, 9 from P12 onwards, 2 from P13 onwards and 3 from P14 onwards

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Summary

Introduction

The specific pattern of a neuronal dendritic arbor determines how that neuron integrates synaptic inputs from multiple, diverse presynaptic cells[1,2,3]. The cerebellar granule cells (GCs) are ideal model neurons for studying the spatiotemporal pattern of dendritic refinement in vivo and revealing the factors that determine stabilization of individual dendrites. This is because, in mice, the majority of GCs undergo dendritic development during the second postnatal week[9], allowing for in vivo investigation of this phenomenon using time-lapse imaging. We found that the number of transient GABAergic synapses, but not glutamatergic synapses, was positively correlated with the length of immature dendrites These results suggest that transient GABAergic inputs to immature dendrites may play a role in their survival, and that the formation of a claw-like ending permanently stabilizes the dendrites

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