Functional Differentiation of Multiple Climbing Fiber Inputs during Synapse Elimination in the Developing Cerebellum

Abstract

We studied how physiological properties of cerebellar climbing fiber (CF) to Purkinje cell (PC) synapses change during developmental transition from multiple to mono CF innervation onto each PC. From P3 to P6, differences in the strengths of multiple CFs became larger. Around P10, each PC was either monoinnervated by one strong CF (CF-mono) or multiply innervated by one strong CF (CF-multi-S) plus a few weaker CFs (CF-multi-W). We show that simultaneous release of multiple vesicles per site occurs normally from CF-multi-S, CF-mono, and mature CFs, but less frequently from CF-multi-W and neonatal CFs. We also present evidence suggesting that weaker CFs with lower probability of multivesicular release would be withdrawn preferentially. The results suggest that differentiation into strong and weak CFs with high and low probabilities of multivesicular release precedes developmental CF synapse elimination.

Type-1 metabotropic glutamate receptor in cerebellar Purkinje cells: a key molecule responsible for long-term depression, endocannabinoid signalling and synapse elimination

“…We show that the paired-pulse ratio, which reflects release probability, is not different among the three types of climbing fibres in a condition in which postsynaptic AMPA receptors should not be saturated (i.e. with a low external Ca 2C concentration; Hashimoto & Kano 2003). Therefore, it is concluded that the number of functional release sites facing a narrow postsynaptic region of Purkinje cell is smaller in the weaker climbing fibres than in the strongest climbing fibre.…”

“…The size of glutamate transients at the synaptic clefts from weaker climbing fibres were consistently smaller than those for the strongest climbing fibres (Hashimoto & Kano 2003). This difference is attributable to the fact that the number of simultaneously released vesicles is smaller (i.e.…”

Guidance Molecules in Axon Pruning and Cell Death

“…Recent data indicate that these arbors are pruned by axosome shedding (Bishop et al 2004), which is associated with lysosomal activities (Song et al 2008). 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).…”

Disturbance of cerebellar synaptic maturation in mutant mice lacking BSRPs, a novel brain‐specific receptor‐like protein family

“…Sagittal cerebellar slices from mice were prepared and whole-cell recording was made from PCs as described previously [10]. 2 .…”