Translocation of a “Winner” Climbing Fiber to the Purkinje Cell Dendrite and Subsequent Elimination of “Losers” from the Soma in Developing Cerebellum

Abstract

Functional neural circuits are formed by eliminating early-formed redundant synapses and strengthening necessary connections during development. In newborn mouse cerebellum, each Purkinje cell (PC) is innervated by multiple climbing fibers (CFs) with similar strengths. Subsequently, a single CF is selectively strengthened by postnatal day 7 (P7). We find that this competition among multiple CFs occurs on the soma before CFs form synapses along dendrites. Notably, in most PCs, the single CF that has been functionally strengthened (the "winner" CF) undergoes translocation to dendrites while keeping its synapses on the soma. Synapses of the weaker CFs (the "loser" CFs) remain around the soma and form "pericellular nests" with synapses of the winner CFs. Then most perisomatic synapses are eliminated nonselectively by P15. Thus, our results suggest that the selective translocation of the winner CF to dendrites in each PC determines the single CF that survives subsequent synapse elimination and persistently innervates the PC.

Postsynaptic P/Q-type Ca 2+ channel in Purkinje cell mediates synaptic competition and elimination in developing cerebellum

“…6 E and F, shaded columns). These results from control mice conform to our previous study reporting that single winner CFs translocate to PC dendrites, whereas "loser" CFs remain around the somata and are subsequently eliminated (11). The results from PCCa v 2.1 KO mice demonstrate that the lack of P/Q-type VDCCs permits multiple CFs to translocate to dendrites and impairs elimination of CF synapses from the soma.…”

“…After selective strengthening of a single CF during the first postnatal week, only the winner CF undergoes translocation to PC dendrites, which starts at around P9 in control mice (11). By marked contrast, our morphological data clearly demonstrate that more than one CF form synaptic contacts on PC dendrites at P12 and P16 in PC-Ca v 2.1 KO mice (Fig.…”

“…From postnatal day 3 (P3) to P7, one CF is selectively strengthened relative to others in each PC (8)(9)(10). Then, the single "winner" CF undergoes translocation to PC dendrites (11). In parallel, redundant CFs are eliminated and most PCs become innervated by single CFs by around P17 in mice (8)(9)(10)12).…”

Guidance Molecules in Axon Pruning and Cell Death

“…The pruning of the climbing fibers also involves elimination of competing arbors and synapses (Hashimoto and Kano 2003;Hashimoto et al 2009;Lohof et al 1996;Mason and Gregory 1984). Interestingly, climbing fiber synapse elimination is associated with structures resembling axosomes (Eckenhoff and Pysh 1979), suggesting that small-scale terminal arbor pruning might operate along similar cellular mechanisms in the PNS and the CNS (Hashimoto et al 2009). …”

Faire et refaire une synapse en choisissant un partenaire

“…Une première hypothèse pour expliquer cette éli-mination sélective vient des observations récentes de Hashimoto et al [14]. Celles-ci suggèrent une compartimentation des signaux responsables de l'élimination synaptique qui affecteraient sans distinction l'ensemble des synapses de fibres grimpantes formées sur le corps cellulaire mais pas les synapses formées sur les dendrites.…”